Trial Outcomes & Findings for NR in Chemo-induced Peripheral Neuropathy (NCT NCT03642990)
NCT ID: NCT03642990
Last Updated: 2023-04-12
Results Overview
The primary outcome variable is defined as no worsening of the grade of peripheral sensory neuropathy as scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines. Per the CTCAE a score of 1 would be assigned in the instance of parethesias or a loss of deep tendon reflexes. A score of 2 would be assigned in the instance of moderate symptoms that limit instrumental activities of daily living. A score of 3 would be assigned in the instance of severe symptoms that limit self-care activities of daily living. Because the outcome measure is defined as no worsening of the grade, it was recorded as either "yes"( i.e. it worsened) or "no" (i.e. it did not worsen).
TERMINATED
PHASE2
5 participants
approximately 4 weeks
2023-04-12
Participant Flow
Subjects were approached at two sites: University of Iowa and Wake Forest Baptist Medical Center. All five subjects enrolled in the study were at Wake Forest Baptist Medical Center.
Seven subjects were screened for enrollment, of whom two were ineligible.
Participant milestones
| Measure |
NIAGEN®)
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
300 mg/Day for One Week
STARTED
|
5
|
|
300 mg/Day for One Week
COMPLETED
|
4
|
|
300 mg/Day for One Week
NOT COMPLETED
|
1
|
|
1000 mg/Day for Weeks 2-12
STARTED
|
4
|
|
1000 mg/Day for Weeks 2-12
COMPLETED
|
0
|
|
1000 mg/Day for Weeks 2-12
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
NIAGEN®)
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
300 mg/Day for One Week
Withdrawal by Subject
|
1
|
|
1000 mg/Day for Weeks 2-12
Physician Decision
|
4
|
Baseline Characteristics
one sample not submitted due to subject testing COVID positive and withdrawing from study
Baseline characteristics by cohort
| Measure |
NIAGEN®)
n=5 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
|
NAD concentration plasma levels
|
27.5 micrograms/ml
n=5 Participants
|
|
1-methyl-nicotinamide plasma levels
|
11.1 ng/ml
n=5 Participants
|
|
paclitaxel plasma levels
|
1629 ng/ml
n=4 Participants • one sample not submitted due to subject testing COVID positive and withdrawing from study
|
PRIMARY outcome
Timeframe: approximately 4 weeksPopulation: Data are reported for the 4 subjects who took at least one dose of NIAGEN. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~14 weeks). If a patient withdrew before completing 12 weeks of treatment, the end of treatment was designated as one week after withdrawal from the study. The longest that any participant was on NIAGEN was three weeks. Therefore, the time frame of the study has been adjusted to \~4 weeks.
The primary outcome variable is defined as no worsening of the grade of peripheral sensory neuropathy as scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 guidelines. Per the CTCAE a score of 1 would be assigned in the instance of parethesias or a loss of deep tendon reflexes. A score of 2 would be assigned in the instance of moderate symptoms that limit instrumental activities of daily living. A score of 3 would be assigned in the instance of severe symptoms that limit self-care activities of daily living. Because the outcome measure is defined as no worsening of the grade, it was recorded as either "yes"( i.e. it worsened) or "no" (i.e. it did not worsen).
Outcome measures
| Measure |
NIAGEN®)
n=4 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Number of Participants With No Worsening in the Grade of Peripheral Sensory Neuropathy as Scored by CTCAE
|
3 Participants
|
SECONDARY outcome
Timeframe: 3 weeksPopulation: Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That subject patient received only 2 doses of taxane over a period of 3 weeks. No patient completed the full 12 weeks of the trial. Therefore, the time frame of the study has been adjusted from the originally envisioned 12 weeks to \~3 weeks.
Quantitate the percentage of patients that experience a dose reduction of paclitaxel or nab-paclitaxel therapy due to neuropathy.
Outcome measures
| Measure |
NIAGEN®)
n=1 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Percentage of Patients in Which Dose of Paclitaxel or Nab-Paclitaxel is Reduced Due to CIPN
|
0 Participants
|
SECONDARY outcome
Timeframe: 3 weeksPopulation: Data are reported for the only subject who received more than 1 dose of taxane chemotherapy before withdrawal from the trial. That patient received only 2 doses of taxane over a period of 3 weeks. The original aim was to assess dose reduction over the 12 weeks of paclitaxel treatment, but no patient completed the 12 weeks of treatment. As the longest that any patient was on NIAGEN was 3 weeks, the time frame has been adjusted accordingly.
Count the number of (i.e. the incidence) of dose reduction events due to neuropathy (each occasion of dose reduction is a separate event);
Outcome measures
| Measure |
NIAGEN®)
n=1 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Number of Dose Reduction Events
|
0 event
|
SECONDARY outcome
Timeframe: 3 weeksPopulation: Data are reported for the 1 subject who received taxane infusions after starting NIAGEN treatment. They received 2 infusions over a period of three weeks of NIAGEN treatment.
Quantitate the total cumulative dose of paclitaxel administered over the 12 weeks.
Outcome measures
| Measure |
NIAGEN®)
n=1 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Total Dose of Paclitaxel Administered
|
200 mg/M^2
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: Data are reported for the three subjects who took at least one dose of NIAGEN and completed the FACT questionnaire. End of treatment was originally defined as within 2 weeks after 12 weeks of NIAGEN treatment ended (i.e. a study duration of \~ 14 weeks). If a patient withdrew before then, the end of treatment was designated as one week after withdrawal. Unfortunately, the longest that any patient was on NIAGEN was three weeks. Therefore, the time frame has been adjusted to \~4 weeks.
Difference in Score on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity questionnaire at the end of treatment; i.e. Score at screening - score at end of treatment. This questionnaire asks 11 questions that are specific to chemotherapy-induced peripheral neuropathies. Maximum score is 44, minimum score is 0. Positive differences indicate a decrease in neuropathy. Negative differences indicate a worsening of neuropathy. Zero means unchanged.
Outcome measures
| Measure |
NIAGEN®)
n=3 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Difference in Score Between Baseline and End of Treatment for the FACT&GOG-NTX Subscale .
|
7 units on a scale
Interval 2.0 to 11.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksPopulation: Data are reported for the three subjects who took at least one dose of NIAGEN and completed the TNS evaluation. No patient completed the full 12 weeks of the trial. Therefore, the measure was made at end of treatment, which was designated as one week after they ceased NIAGEN treatment. The longest any one patient was on NIAGEN was three weeks. Hence the time frame was adjusted to 4 weeks.
Exploratory analysis of ability of the clinical version of the Total Neuropathy Score questionnaire to detect changes in CIPN severity over time. Unlike the CTCAE or the FACT\&GOG-NTX questionnaires, the TNS is a patient reported outcome measure. HIghest score (worse neuropathy is 24, lowest score is 0. Outcome assessed difference between end of treatment and screening. A positive number indicates improvement in neuropathy
Outcome measures
| Measure |
NIAGEN®)
n=3 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Difference in Total Neuropathy Score Between Screening and End of Treatment
|
2 score on a scale
Interval 0.0 to 5.0
|
POST_HOC outcome
Timeframe: up to 3 weeksPopulation: Data are reported for three subjects in which paclitaxel levels were obtained before NIAGEN and after NIAGEN treatment, which ranged from one to three weeks. The plasma concentration for the last blood sample obtained after NIAGEN treatment
Paclitaxel levels in plasma were measured \~30 min after each infusion of taxane. This was undertaken to ascertain whether NIAGEN altered plasma levels of paclitaxel because increases or decreases in plasma levels of paclitaxel by itself could lead to an apparent worsening or improvement, respectively, in CIPN and confound interpretation of NIAGEN's effect.
Outcome measures
| Measure |
NIAGEN®)
n=3 Participants
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Plasma Concentration of Paclitaxel After NIAGEN Treatment Began
|
810 ng/ml
Interval 259.7 to 1525.0
|
Adverse Events
NIAGEN®)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
NIAGEN®)
n=5 participants at risk
Daily oral administration of nicotinamide riboside 300 mg (150 mg a.m. and p.m.) for one week with dose escalation to 1000 mg (500 mg a.m. and p.m.) for remaining 11 weeks.
Nicotinamide Riboside: Capsule
|
|---|---|
|
Vascular disorders
flushing
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Gastrointestinal disorders
Nausea
|
80.0%
4/5 • Number of events 5 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Gastrointestinal disorders
mucositis oral
|
20.0%
1/5 • Number of events 2 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Gastrointestinal disorders
diarrhea
|
60.0%
3/5 • Number of events 3 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Gastrointestinal disorders
dyspepsia
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Gastrointestinal disorders
vomiting
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Nervous system disorders
headache
|
60.0%
3/5 • Number of events 3 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Nervous system disorders
peripheral sensory neuropathy
|
40.0%
2/5 • Number of events 5 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
dizziness
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Nervous system disorders
peripheral motor neuropathy
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Metabolism and nutrition disorders
hypocalcemia
|
40.0%
2/5 • Number of events 2 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Metabolism and nutrition disorders
hypercalcemia
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Metabolism and nutrition disorders
hypokalemia
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
General disorders
fatigue
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
General disorders
localized edema
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
General disorders
pain
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Investigations
white blood cell decreased
|
40.0%
2/5 • Number of events 4 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Investigations
alanine aminotransferase increased
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Investigations
lymphocyte count decreased
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Blood and lymphatic system disorders
anemia
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Cardiac disorders
chest pain
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Infections and infestations
upper respiratory infection
|
20.0%
1/5 • Number of events 3 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
20.0%
1/5 • Number of events 1 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
nasal congestion
|
20.0%
1/5 • Number of events 3 • Up to six months after end of treatment (typically 7 months total)
Subjects were queried for adverse events by phone interview 1, 3 and 6 months after end of treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place