Trial Outcomes & Findings for Study of Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in HCT Recipients (NCT NCT02420223)
NCT ID: NCT02420223
Last Updated: 2021-06-07
Results Overview
Expression (up or down regulation) of genes involved in the stress response can be modulated through the beta-adrenergic pathway. The log2 RNA abundance is a means to normalize results to determine whether a gene is up regulated (value greater than 1) or down regulated (value less than 1). Differential change in log2 RNA abundance is defined by the fold change (FC) as log2FC=Log2(B)-Log2(A). Logarithmic measures are unitless. The change in the measure between two time points determines whether a gene has up-or down-regulated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Baseline (Pre-Transplant); 4 weeks post-transplant
Results posted on
2021-06-07
Participant Flow
Participant milestones
| Measure |
Propranolol
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Overall Study
STARTED
|
12
|
13
|
|
Overall Study
COMPLETED
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Propranolol
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
Baseline Characteristics
Study of Propranolol to Decrease Gene Expression of Stress-Mediated Beta-Adrenergic Pathways in HCT Recipients
Baseline characteristics by cohort
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
16 Participants
n=35 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 9.1 • n=39 Participants
|
63 years
STANDARD_DEVIATION 8.6 • n=41 Participants
|
61 years
STANDARD_DEVIATION 8.6 • n=35 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=39 Participants
|
5 Participants
n=41 Participants
|
10 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=39 Participants
|
8 Participants
n=41 Participants
|
15 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
6 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=39 Participants
|
11 Participants
n=41 Participants
|
19 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=39 Participants
|
13 participants
n=41 Participants
|
25 participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Baseline (Pre-Transplant); 4 weeks post-transplantExpression (up or down regulation) of genes involved in the stress response can be modulated through the beta-adrenergic pathway. The log2 RNA abundance is a means to normalize results to determine whether a gene is up regulated (value greater than 1) or down regulated (value less than 1). Differential change in log2 RNA abundance is defined by the fold change (FC) as log2FC=Log2(B)-Log2(A). Logarithmic measures are unitless. The change in the measure between two time points determines whether a gene has up-or down-regulated.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Beta-adrenergically Mediated Gene Expression (Change From Baseline)
|
-0.407 Unitless
Standard Error 0.165
|
0.0099 Unitless
Standard Error 0.103
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: One propranolol subject was discontinued due to symptomatic hypotension. Two control subjects were discontinued doe to initiation of beta-blocker therapy for cardiac arrhythmia.
This measure will be assessed using the Hospital Anxiety and Depression Scale (HADS). The HADS scale includes fourteen 4-response Likert-scale questions graded 0 to 3. Seven questions are specific to depression; 7 questions are specific to anxiety. The score is the total of the responses in their respective categories. Lower scores indicated less depression and/or anxiety. Scores 0-7 indicate normal status; scores 8-10 suggest borderline abnormal status; and scores 11-21 indicate abnormal status. Only anxiety scores are presented.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Patient-reported Depression and Anxiety Scores
Baseline Anxiety Score
|
7.3 units on a scale
Standard Deviation 3.5
|
7.4 units on a scale
Standard Deviation 3.7
|
|
Patient-reported Depression and Anxiety Scores
4-Week Anxiety Score
|
4.4 units on a scale
Standard Deviation 2.3
|
5.2 units on a scale
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: 4 weeksNumber of subjects experiencing any of: fever, diarrhea or rash requiring steroid intervention within 48 hours before or after neutrophil recovery.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Number of Subjects Experiencing Engraftment Syndrome as a Function of Beta-blocker Administration
|
6 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: 4 weeks after transplantThis measure is the mean time to the beginning of three consecutive days where the neutrophil count (absolute neutrophil count) was 500 cells/mm\^3 (0.5 x 10\^9/L) or greater.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Time (Days) to Neutrophil Engraftment
|
10.5 Days
Standard Deviation 1.0
|
11.9 Days
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: 4 weeksThis measure is the mean time to the beginning of three consecutive days where the platelet count is at least 20,000/mm\^3 (20 x 10\^9/L) unsupported by a platelet transfusion.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Time (Days) to Platelet Engraftment
|
16.6 Days
Standard Deviation 4.1
|
19.6 Days
Standard Deviation 5.4
|
SECONDARY outcome
Timeframe: Up to 100 days after transplantThis measure is the number of subjects diagnosed with culture-positive infection or neutropenic fever greater than 100.4 degrees Fahrenheit.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Number of Participants Diagnosed With Culture-positive Infection or Neutropenic Fever Greater Than 100.4 Degrees Fahrenheit
|
1 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: 100 days after transplantThis measure is the number of participants experiencing a response defined by the International Uniform Response Criteria as: very good partial response (VGPR) or better (near complete response (nCR), complete response (CR), and stringent CR (sCR) according to at day 100 post-Hematopoietic Cell Transplant.
Outcome measures
| Measure |
Propranolol
n=12 Participants
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 Participants
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Number of Participants With Myeloma Response as a Function of Beta-blocker Administration
Stable Disease
|
1 Participants
|
0 Participants
|
|
Number of Participants With Myeloma Response as a Function of Beta-blocker Administration
Partial Response
|
5 Participants
|
5 Participants
|
|
Number of Participants With Myeloma Response as a Function of Beta-blocker Administration
Very Good Partial Response
|
5 Participants
|
5 Participants
|
|
Number of Participants With Myeloma Response as a Function of Beta-blocker Administration
Complete Response
|
1 Participants
|
3 Participants
|
Adverse Events
Propranolol
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Control Arm
Serious events: 3 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Propranolol
n=12 participants at risk
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 participants at risk
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
General disorders
Edema of limb
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
General disorders
Fever
|
8.3%
1/12 • Number of events 1 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Infections and infestations
Eye infection
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
Other adverse events
| Measure |
Propranolol
n=12 participants at risk
Patient's randomized to the Propranolol arm will be starting 7 days prior to transplant and continuing through 28 days post-transplant. Propranolol will start at 20mg twice daily and will be titrated to 40mg twice daily as tolerated. Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for up to 7 total weeks for patient's on the Propranolol arm.
Propranolol
|
Control Arm
n=13 participants at risk
Both groups will come back to the hospital weekly in order to assess items such as patient's level of anxiety, depression, your adherence, and also to monitor for side effects. The patient's will complete questionnaires during your visit. These will take approximately 15 minutes to complete. This will continue for 6 total weeks for patient's on the control arm.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.3%
1/12 • Number of events 1 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Investigations
Creatinine increased
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
4/12 • Number of events 4 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.3%
1/12 • Number of events 1 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Vascular disorders
Flushing
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/12 • 100 Days
|
23.1%
3/13 • Number of events 3 • 100 Days
|
|
Vascular disorders
Hypertension
|
8.3%
1/12 • Number of events 1 • 100 Days
|
46.2%
6/13 • Number of events 6 • 100 Days
|
|
Metabolism and nutrition disorders
Hypokalemia
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Vascular disorders
Hypotension
|
25.0%
3/12 • Number of events 3 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
2/12 • Number of events 2 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.3%
1/12 • Number of events 1 • 100 Days
|
0.00%
0/13 • 100 Days
|
|
Infections and infestations
Periorbital infection
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
8.3%
1/12 • Number of events 1 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/12 • 100 Days
|
15.4%
2/13 • Number of events 2 • 100 Days
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/12 • 100 Days
|
7.7%
1/13 • Number of events 1 • 100 Days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place