Trial Outcomes & Findings for Treating Negative Affect in Low Back Pain Patients (NCT NCT04747314)
NCT ID: NCT04747314
Last Updated: 2026-08-28
Results Overview
To create the "composite responder" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the "composite responder" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The "composite responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1. A participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in each domain. The primary outcome is the rate of response vs. non-response on the "Composite Responder" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
308 participants
Primary outcome timeframe
Baseline vs. 4th month of study
Results posted on
2026-08-28
Participant Flow
Participant milestones
| Measure |
Antidepressant (AD) Months 1-4
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR) Months 1-4
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR) Months 1-8
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant → EFAR (Non-Responder Re-Randomized to EFAR) Months 5-8
Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized to receive Enhanced Fear Avoidance Rehabilitation (EFAR) for an additional 4 months. EFAR included up to 8 one-hour physical therapy sessions, pain education, and activities individualized by trained therapists and focused on gradual exposure to feared movements or activities.
|
Antidepressant → Antidepressant (Non-Responder Re-Randomized to AD) Months 5-8
Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized, continued the antidepressant treatment for an additional 4 months (total duration: 8 months), with ongoing monitoring and dose adjustment as needed.
|
EFAR → Antidepressant (Non-Responder Re-Randomized to AD) Months 5-8
Only participants who agreed to be re-randomized and were identified as non-responders at 4 months were re-randomized to receive antidepressant (AD) treatment for an additional 4 months. Antidepressant treatment included medication management by a nurse practitioner and psychiatrist, use of the Antidepressant Treatment History Form (ATHF) and medication flowchart, check-in visits every 4 weeks, and weekly participant assessments to monitor response and tolerability.
|
EFAR → EFAR (Non-Responder Re-Randomized to EFAR) Months 5-8
Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized to continue EFAR for an additional 4 months (total duration: 8 months).
|
AD Responders Months 5-8
Responders in the AD treatment will continue with the same AD treatment until the end of the study, which is month 8.
|
EFAR Responders - Months 5-8
Responders to the EFAR treatment will continue with the same treatment and will be given an individualized home treatment program that will emphasize exercises they can perform a prescribed number of times a week during the remaining 4 months of the study.
|
|---|---|---|---|---|---|---|---|---|---|
|
Phase 1
STARTED
|
100
|
103
|
105
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1
COMPLETED
|
73
|
68
|
72
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1
NOT COMPLETED
|
27
|
35
|
33
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2
STARTED
|
0
|
0
|
72
|
26
|
24
|
27
|
24
|
1
|
1
|
|
Phase 2
COMPLETED
|
0
|
0
|
55
|
26
|
19
|
23
|
20
|
1
|
1
|
|
Phase 2
NOT COMPLETED
|
0
|
0
|
17
|
0
|
5
|
4
|
4
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Treating Negative Affect in Low Back Pain Patients
Baseline characteristics by cohort
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Total
n=213 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Sex: Female, Male
Female
|
46 Participants
n=31 Participants
|
51 Participants
n=49 Participants
|
43 Participants
n=80 Participants
|
140 Participants
n=29 Participants
|
|
Age, Continuous
|
52.5 Years
n=31 Participants
|
52.9 Years
n=49 Participants
|
46.5 Years
n=80 Participants
|
50.0 Years
n=29 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=31 Participants
|
17 Participants
n=49 Participants
|
29 Participants
n=80 Participants
|
73 Participants
n=29 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=31 Participants
|
5 Participants
n=49 Participants
|
6 Participants
n=80 Participants
|
16 Participants
n=29 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
68 Participants
n=31 Participants
|
61 Participants
n=49 Participants
|
62 Participants
n=80 Participants
|
191 Participants
n=29 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=31 Participants
|
2 Participants
n=49 Participants
|
4 Participants
n=80 Participants
|
6 Participants
n=29 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=31 Participants
|
0 Participants
n=49 Participants
|
2 Participants
n=80 Participants
|
4 Participants
n=29 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=31 Participants
|
2 Participants
n=49 Participants
|
2 Participants
n=80 Participants
|
5 Participants
n=29 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=31 Participants
|
0 Participants
n=49 Participants
|
0 Participants
n=80 Participants
|
0 Participants
n=29 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=31 Participants
|
13 Participants
n=49 Participants
|
8 Participants
n=80 Participants
|
35 Participants
n=29 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=31 Participants
|
46 Participants
n=49 Participants
|
57 Participants
n=80 Participants
|
154 Participants
n=29 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=31 Participants
|
4 Participants
n=49 Participants
|
2 Participants
n=80 Participants
|
8 Participants
n=29 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=31 Participants
|
3 Participants
n=49 Participants
|
1 Participants
n=80 Participants
|
7 Participants
n=29 Participants
|
|
Region of Enrollment
United States
|
73 participants
n=31 Participants
|
68 participants
n=49 Participants
|
72 participants
n=80 Participants
|
213 participants
n=29 Participants
|
PRIMARY outcome
Timeframe: Baseline vs. 4th month of studyPopulation: Number of responders in each group
To create the "composite responder" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the "composite responder" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The "composite responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1. A participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in each domain. The primary outcome is the rate of response vs. non-response on the "Composite Responder" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes).
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
"Composite Responder", Involving the Domains of Pain, Function, and Depression. See "Other Pre-Specified Outcomes" for Description of These Sub-components.
|
11 Participants
|
8 Participants
|
20 Participants
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
The PROMIS Short Form v1.1 - Pain Interference 4a will assess self-reported consequences of pain with 4 questions ranked on a 5-point scale, from "not at all" to "very much". The minimum raw summed score is 4 and the maximum score is 20. This is converted to a T score. A lower T-scores suggest better outcomes. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. Outcomes will be measured and compared between the 3 treatment groups.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change From Baseline Pain Interference at 4 Months Using PROMIS
Baseline
|
64.0 T score
Interval 61.3 to 67.5
|
65.0 T score
Interval 61.3 to 68.0
|
62.4 T score
Interval 58.5 to 68.2
|
|
Change From Baseline Pain Interference at 4 Months Using PROMIS
Month 4
|
60.2 T score
Interval 57.0 to 64.4
|
61.0 T score
Interval 57.9 to 66.2
|
58.5 T score
Interval 54.8 to 63.3
|
|
Change From Baseline Pain Interference at 4 Months Using PROMIS
Difference
|
-4.12 T score
Interval -6.62 to -0.73
|
-2.41 T score
Interval -5.16 to -0.24
|
-3.79 T score
Interval -7.21 to -0.68
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
The PROMIS Short Form v1.0 - Anxiety 4a will assess self-reported symptoms with 4 questions ranked on a 5-point scale, from "never" to "always". The minimum raw score is a 4 and the maximum is 20.. These are converted to a T score. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure. Lower T-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change From Baseline Anxiety at 4 Months Using PROMIS
Month 4
|
55.8 T score
Interval 52.4 to 61.2
|
61.2 T score
Interval 56.0 to 65.2
|
56.7 T score
Interval 51.7 to 61.5
|
|
Change From Baseline Anxiety at 4 Months Using PROMIS
Baseline
|
62.6 T score
Interval 57.6 to 66.2
|
63.0 T score
Interval 59.5 to 68.5
|
63.5 T score
Interval 58.6 to 68.4
|
|
Change From Baseline Anxiety at 4 Months Using PROMIS
Difference
|
-5.27 T score
Interval -9.2 to -2.4
|
-2.99 T score
Interval -5.99 to 0.06
|
-5.7 T score
Interval -11.52 to -1.93
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
The PROMIS Short Form v1.0 - Sleep Disturbance 6a self-reported perceptions of sleep quality and sleep depth with 6 questions ranked on a 5-point scale. The minimum raw summed score is 6 and the maximum score is 30. This is converted to a T score. Lower T scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change From Baseline Sleep Disturbance at 4 Months Using PROMIS
Baseline
|
57.5 T score
Interval 53.6 to 62.8
|
58.0 T score
Interval 54.3 to 62.3
|
58.5 T score
Interval 54.4 to 63.6
|
|
Change From Baseline Sleep Disturbance at 4 Months Using PROMIS
Month 4
|
53.9 T score
Interval 49.8 to 58.1
|
56.1 T score
Interval 53.2 to 60.3
|
52.8 T score
Interval 46.6 to 58.8
|
|
Change From Baseline Sleep Disturbance at 4 Months Using PROMIS
Difference
|
-3.15 T score
Interval -6.73 to 0.24
|
-0.88 T score
Interval -5.33 to 1.06
|
-3.59 T score
Interval -9.71 to -1.12
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsThe subject's impression of the impact of the treatment on their pain and function will be measured with a 7-item scale (1 = very much worse, 2 = much worse, 3 = minimally worse, 4 = no change, 5 = minimally improved, 6 = much improved, 7 = very much improved). This is the percentage reporting "very much improved" or "much improved" at the end of Phase 1. We averaged their PGIC ratings in the 4th month.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change From Baseline Subject's Perception of Change From Treatment at 4 Months Using Patient Global Impression of Change (PGIC)
|
27 Participants
|
21 Participants
|
37 Participants
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
Using PainDetect, we will compare changes in neuropathic pain symptoms from baseline to 4 months. PainDetect is scored from 0-38 and based on ratings to symptom items scored from '0' (never) to '5' (very strongly). Lower scores are better.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Neuropathic Pain Symptoms Change, Baseline vs. 4 Months
Baseline
|
15.0 score on a scale
Interval 10.0 to 19.0
|
14.5 score on a scale
Interval 10.0 to 21.0
|
13.2 score on a scale
Interval 9.2 to 19.0
|
|
Neuropathic Pain Symptoms Change, Baseline vs. 4 Months
Month 4
|
13.0 score on a scale
Interval 6.0 to 18.0
|
11.0 score on a scale
Interval 6.0 to 18.2
|
9.0 score on a scale
Interval 5.0 to 17.0
|
|
Neuropathic Pain Symptoms Change, Baseline vs. 4 Months
Difference
|
-2.5 score on a scale
Interval -5.5 to 0.0
|
-2.25 score on a scale
Interval -7.0 to 0.75
|
-3.5 score on a scale
Interval -6.0 to 0.5
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
Using the Fear Avoidance Beliefs Questionnaire, Physical Activities Items, subjects rate from '0' (completely disagree) to '6' (completely agree) five physical activities which may make their pain worse. The items are summed to produce the total score. The minimum score is a 0 and the maximum is a 30. Lower scores are better.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Fear Avoidance Beliefs, Baseline vs. 4 Months
Month 4
|
17.5 score on a scale
Interval 13.0 to 22.0
|
17.0 score on a scale
Interval 10.0 to 22.0
|
14.5 score on a scale
Interval 10.2 to 21.0
|
|
Fear Avoidance Beliefs, Baseline vs. 4 Months
Baseline
|
20.5 score on a scale
Interval 15.5 to 24.0
|
18.8 score on a scale
Interval 14.5 to 22.6
|
19.8 score on a scale
Interval 16.0 to 24.0
|
|
Fear Avoidance Beliefs, Baseline vs. 4 Months
Difference
|
-1.75 score on a scale
Interval -5.38 to 1.38
|
-1.5 score on a scale
Interval -5.62 to 1.5
|
-3.5 score on a scale
Interval -10.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
This measure assesses the degree of widespread pain. 20 body regions are rated by patient as having pain or not. The minumum scores is a 0 and the maximum is a 20. The number of regions is summed to give the total score. Lower scores are better.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Widespread Pain Index
Difference
|
-0.5 score on a scale
Interval -2.0 to 0.5
|
-0.5 score on a scale
Interval -2.0 to 1.5
|
-1 score on a scale
Interval -2.5 to 0.5
|
|
Widespread Pain Index
Baseline
|
5.5 score on a scale
Interval 3.5 to 8.5
|
4.5 score on a scale
Interval 3.5 to 7.5
|
5.5 score on a scale
Interval 3.5 to 8.5
|
|
Widespread Pain Index
Month 4
|
5.0 score on a scale
Interval 3.0 to 8.0
|
4.0 score on a scale
Interval 3.0 to 8.0
|
5.0 score on a scale
Interval 2.0 to 7.0
|
SECONDARY outcome
Timeframe: Baseline vs. 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
The PROMIS short form v. 1.0 for Fatigue consists of 2 items rated from 1-5, from "not at all" to "very much." The minimum raw score is a 2 and the maximum is a 10. The raw score is summed and converted to a T score. Lower T scores are better. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \>60 suggests moderately elevated levels of the measure.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change in PROMIS Fatigue Score From Baseline vs. 4 Months
Baseline
|
61.8 T score
Interval 57.1 to 66.7
|
62.9 T score
Interval 57.9 to 66.5
|
61.7 T score
Interval 56.9 to 68.8
|
|
Change in PROMIS Fatigue Score From Baseline vs. 4 Months
Month 4
|
56.3 T score
Interval 51.0 to 60.8
|
59.0 T score
Interval 54.4 to 65.2
|
56.7 T score
Interval 49.3 to 63.8
|
|
Change in PROMIS Fatigue Score From Baseline vs. 4 Months
Difference
|
-6.27 T score
Interval -10.03 to -0.47
|
-2.76 T score
Interval -5.91 to 0.72
|
-4.57 T score
Interval -9.7 to -0.04
|
SECONDARY outcome
Timeframe: Baseline to 4 monthsPopulation: These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.
Overall symptom severity is rated 0-10. Lower scores are better.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
WPI Symptom Severity Score
Baseline
|
7.0 score on a scale
Interval 5.0 to 8.0
|
7.0 score on a scale
Interval 5.5 to 8.0
|
6.5 score on a scale
Interval 4.9 to 8.0
|
|
WPI Symptom Severity Score
Month 4
|
6.0 score on a scale
Interval 4.0 to 7.0
|
6.0 score on a scale
Interval 5.0 to 8.0
|
5.0 score on a scale
Interval 3.0 to 7.0
|
|
WPI Symptom Severity Score
Difference
|
-1 score on a scale
Interval -2.5 to 0.5
|
-0.5 score on a scale
Interval -1.62 to 0.5
|
-1.5 score on a scale
Interval -2.38 to 0.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline vs. 4 monthsPopulation: This is a proportion of responders analysis, as described in more detail above.
The PROMIS Short Form v2.0 - Physical Function 6b questionnaire will assess self-reported capability with 6 qualitatively scaled questions ranked on a 5-point scale, from "without any difficulty" to "unable to do" or "not at all" to "cannot do." The minimum raw summed score is 6 and the maximum score is 30. Lower t-scores suggest better outcomes. A responder analysis was used as a subcomponent of the "composite responder" primary outcome. A "physical function responder" had to have at least a 3-point improvement in T score at 4 months vs. baseline. The "physical function responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change in Physical Function Using PROMIS Short Form 2.0. Function is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.
|
34 Participants
Interval 33.4 to 39.7
|
31 Participants
Interval 34.1 to 39.3
|
39 Participants
Interval 34.1 to 42.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline vs. 4 monthsPopulation: This is a responder analysis for the number of responders in each group.
The PROMIS Numeric Rating Scale v1.0 for average pain intensity-- Pain Intensity 1a questionnaire will assess how much a person hurts on average over the past 7 days, with a question ranked on a 11-point scale, from "0 = no pain" to "10 = worst imaginable pain." The minimum raw summed score is 0 and the maximum score is 10. Lower scores suggest lower pain intensity and better outcomes. To be a "pain responder" a subject had to have at least 30% improvement in pain. The "pain responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change in Pain Intensity Using PROMIS. Pain is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.
|
22 Participants
Interval 5.5 to 7.0
|
15 Participants
Interval 6.0 to 7.5
|
32 Participants
Interval 5.0 to 7.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline vs. 4 monthsPopulation: A responder analysis of the numbers of patient responders in each group
The PROMIS Short Form v1.0 - Depression 4a will assess self-reported negative mood and views of self with 4 questions ranked on a 5-point scale, from "never" to "always". The minimum raw summed score is 4 and the maximum score is 20. Lower T scores suggest better outcomes. A T score improvement of at least 5 points is considered a responder. The "depression responder" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.
Outcome measures
| Measure |
Antidepressant (AD)
n=73 Participants
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=68 Participants
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=72 Participants
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Change in Depression Using PROMIS. Depression is Part of the "Composite Responder" Measure. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.
|
48 Participants
Interval 57.1 to 66.5
|
29 Participants
Interval 58.8 to 64.1
|
47 Participants
Interval 56.2 to 63.1
|
Adverse Events
Antidepressant (AD)
Serious events: 12 serious events
Other events: 0 other events
Deaths: 0 deaths
Enhanced Fear Avoidance Rehabilitation (EFAR)
Serious events: 7 serious events
Other events: 0 other events
Deaths: 0 deaths
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Antidepressant (AD)
n=100 participants at risk
Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
|
Enhanced Fear Avoidance Rehabilitation (EFAR)
n=103 participants at risk
Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)
n=105 participants at risk
Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.
Antidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.
The Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.
Enhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.
|
|---|---|---|---|
|
Hepatobiliary disorders
Gallbladder Surgery
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Injury, poisoning and procedural complications
Hospitalization for head & neck pain from hitting head
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Nervous system disorders
Hospitalization for MS Flare
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.95%
1/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Respiratory, thoracic and mediastinal disorders
Hospitalization for Pneumonia
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.95%
1/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Gastrointestinal disorders
Hospitalization for chest and abdominal pain
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Gastrointestinal disorders
Hospitalization for gastroenteritis
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Reproductive system and breast disorders
Hospitalized for elective laparoscopic hysterectomy
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Surgical and medical procedures
Hospitalized for elective back surgery
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.95%
1/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Injury, poisoning and procedural complications
Admission for severe pain in left flank after fall at home
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Renal and urinary disorders
Kidney stone extraction
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Renal and urinary disorders
Admission for kidney stone symptoms
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Number of events 2 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Musculoskeletal and connective tissue disorders
Admission for knee pain
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Nervous system disorders
Epileptic Seizures
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Musculoskeletal and connective tissue disorders
Admission for lumbar decompression
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Nervous system disorders
Admission for cauda equina syndrome
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Cardiac disorders
Hospitalization due to low ejection fraction
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Musculoskeletal and connective tissue disorders
Hospitalization due to whiplash injury
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.95%
1/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Hepatobiliary disorders
Hospitalization due to alcohol detox
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.97%
1/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Psychiatric disorders
Hospitalization due to psychiatric episode
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Endocrine disorders
Hospitalization due to transsphenoidal resections of a pituitary macroadenoma
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Nervous system disorders
Hospitalization due to dizziness and ataxia
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Respiratory, thoracic and mediastinal disorders
Hospitalization due to shortness of breath
|
1.0%
1/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
|
Renal and urinary disorders
Hospitalization due to pyelitis
|
0.00%
0/100 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.00%
0/103 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
0.95%
1/105 • Adverse events were monitored for each participant during Phase 1 for 4 months and for an additional 4 months during Phase 2 in participants who were re-randomized and continued in the study.
An adverse event is any unfavorable and unintended diagnosis, sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the study intervention, which may or may not be related to the intervention. AEs include any new events not present during the pre-intervention period or events that were present during the pre-intervention period which increased in severity.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place