Trial Outcomes & Findings for Nicotinamide Riboside in LVAD Recipients (NCT NCT03727646)
NCT ID: NCT03727646
Last Updated: 2024-09-20
Results Overview
Participants experiencing adverse events during the time they are on the study drug. Regarding time frame: Day 1 is the first day that the study subjects start taking the study drug (NR). The participants stop taking the study drug on the day before his/her LVAD surgery (between Days 6 and 14).
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
5 participants
Primary outcome timeframe
from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)
Results posted on
2024-09-20
Participant Flow
Participant milestones
| Measure |
Open-label Nicotinamide Riboside
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
0
|
|
Overall Study
COMPLETED
|
4
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Open-label Nicotinamide Riboside
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Nicotinamide Riboside in LVAD Recipients
Baseline characteristics by cohort
| Measure |
Open-label Nicotinamide Riboside
n=5 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
—
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
35.4 years
n=5 Participants
|
—
|
35.4 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
—
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
—
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
—
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
—
|
5 participants
n=5 Participants
|
|
LV Ejection Fraction
|
20.6 %
n=5 Participants
|
—
|
20.6 %
n=5 Participants
|
PRIMARY outcome
Timeframe: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)Population: We did not enroll any baseline control subjects.
Participants experiencing adverse events during the time they are on the study drug. Regarding time frame: Day 1 is the first day that the study subjects start taking the study drug (NR). The participants stop taking the study drug on the day before his/her LVAD surgery (between Days 6 and 14).
Outcome measures
| Measure |
Open-label Nicotinamide Riboside
n=4 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Number of Participates Experiencing Treatment-Emergent Adverse Events (Safety and Tolerability)
|
2 Participants
|
—
|
PRIMARY outcome
Timeframe: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)Population: We did not have the funds to enroll baseline control subjects.
Comparison of maximal mitochondrial respiration in PBMCs on the Day of LVAD Surgery Pre- vs Post-NR Administration
Outcome measures
| Measure |
Open-label Nicotinamide Riboside
n=4 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Pre/Post NR Comparison of Maximal Mitochondrial Respiration in PBMCs
Pre-NR
|
140.8 pmole/min/million cells (O2 consump rate
Standard Deviation 31.6
|
—
|
|
Pre/Post NR Comparison of Maximal Mitochondrial Respiration in PBMCs
Post-NR
|
317.8 pmole/min/million cells (O2 consump rate
Standard Deviation 107.6
|
—
|
SECONDARY outcome
Timeframe: from Day 1 receiving NR to the day before LVAD surgery (between Day 6-Day 14)Change in whole blood NAD+ levels from Baseline to Day of Surgery in NR-treated participants
Outcome measures
| Measure |
Open-label Nicotinamide Riboside
n=4 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
n=4 Participants
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Effect of NR on Whole Blood NAD+ Levels
|
40.625 ug/mL
Standard Deviation 11.19266873
|
18.025 ug/mL
Standard Deviation 2.662548904
|
SECONDARY outcome
Timeframe: Data collected 6-14 days after study intervention (oral NR) has been initiated.Population: The control subjects were unfortunately not enrolled so we were unable to make the intergroup comparison.
Comparison of mitochondrial respiration (Seahorse assay) in isolated peripheral blood mononuclear cells (PBMCs) on the Day of LVAD Surgery in NR-treated vs. historical control patients
Outcome measures
| Measure |
Open-label Nicotinamide Riboside
n=4 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Between-group Comparison of Mitochondrial Respiration (Seahorse Assay) in Isolated Peripheral Blood Mononuclear Cells (PBMCs)
|
317.7895265 pmole/min/million cells (O2 consump rate
Standard Deviation 107.6126397
|
—
|
SECONDARY outcome
Timeframe: Data collected 6-14 days after study intervention (oral NR) has been initiated.Population: We unfortunately did not enroll any control subjects, hence were unable to make the intergroup comparison.
Comparison of whole blood NAD+ levels on the Day of LVAD Surgery in NR-treated vs. historical control patients
Outcome measures
| Measure |
Open-label Nicotinamide Riboside
n=4 Participants
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Between-group Comparison of Whole Blood NAD+ Levels
|
40.625 ug/mL
Standard Deviation 11.19266873
|
—
|
Adverse Events
Open-label Nicotinamide Riboside
Serious events: 2 serious events
Other events: 0 other events
Deaths: 1 deaths
Baseline Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-label Nicotinamide Riboside
n=5 participants at risk
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide riboside: nicotinamide riboside supplied as 250mg capsules
|
Baseline Controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
|
|---|---|---|
|
Cardiac disorders
Cardiac Arrest
|
20.0%
1/5 • Number of events 1 • from Day 1 receiving NR to 30 days post-LVAD implantation.
The study patients were on NR for a short period of time and it is extremely difficult to tease out their symptoms of terminal HF versus those from NR administration.
|
—
0/0 • from Day 1 receiving NR to 30 days post-LVAD implantation.
The study patients were on NR for a short period of time and it is extremely difficult to tease out their symptoms of terminal HF versus those from NR administration.
|
|
Nervous system disorders
Death
|
20.0%
1/5 • Number of events 1 • from Day 1 receiving NR to 30 days post-LVAD implantation.
The study patients were on NR for a short period of time and it is extremely difficult to tease out their symptoms of terminal HF versus those from NR administration.
|
—
0/0 • from Day 1 receiving NR to 30 days post-LVAD implantation.
The study patients were on NR for a short period of time and it is extremely difficult to tease out their symptoms of terminal HF versus those from NR administration.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60