Phase 3
N=90
Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease
Peripheral Artery Disease
Bottom Line
View on ClinicalTrials.gov: NCT03743636 ↗Enrolled (actual)
90
Serious AEs
23.3%
Results posted
Jan 2025
Primary outcome: Primary: Six-minute Walk Distance (NR Alone vs. Placebo) — -6.93; 7.00; -10.58 meters — p=0.0775
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Nicotinamide riboside (Drug); Resveratrol (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Northwestern University
- Primary completion
- May 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Six-minute Walk Distance (NR Alone vs. Placebo) |
2.99; 4.78; -17.64 | 0.0294 sig |
| PRIMARY Six-minute Walk Distance (NR/Resveratrol vs. Placebo) |
2.99; 4.78; -17.64 | 0.0336 sig |
| SECONDARY Six-minute Walk Distance (NR Alone vs. Placebo) |
2.99; 4.78; -17.64 | 0.0294 sig |
| SECONDARY Six-minute Walk Distance (NR/Resveratrol vs. Placebo) |
2.99; 4.78; -17.64 | 0.0336 sig |
| SECONDARY Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) |
-6.93; 7.00; -10.58 | 0.8797 |
| SECONDARY Six-minute Walk Distance (NR/Resveratrol vs. NR Alone) |
-6.93; 7.00; -10.58 | 0.8797 |
| SECONDARY Maximal Treadmill Walking Time (NR Alone vs. Placebo) |
0.57; 0.89; -1.17 | 0.0752 |
| SECONDARY Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo) |
0.82; -1.24; 5.86 | 0.8703 |
| SECONDARY Physical Activity (NR Alone vs. Placebo) |
-7743; 4094; -6901 | 0.1402 |
| SECONDARY Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo) |
0.57; 0.89; -1.17 | 0.1249 |
| SECONDARY Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo) |
0.82; -1.24; 5.86 | 0.8039 |
| SECONDARY Physical Activity (NR/Resveratrol vs. Placebo) |
-7743; 4094; -6901 | 0.5352 |
| SECONDARY Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone) |
0.57; 0.89; -1.17 | 0.5777 |
| SECONDARY Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone) |
0.82; -1.24; 5.86 | 0.3662 |
| SECONDARY Physical Activity (NR/Resveratrol vs. NR Alone) |
-7743; 4094; -6901 | 0.8866 |
| SECONDARY Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) |
-14.29; -0.24 | 0.1195 |
| SECONDARY Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo) |
-14.29; -0.24 | 0.1195 |
| SECONDARY Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo) |
-1.33; 0.73 | 0.0752 |
| SECONDARY Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo) |
6.89; -0.21 | 0.8703 |
| SECONDARY Physical Activity (NR/Resveratrol or NR Alone vs. Placebo) |
-12819; -1824 | 0.1402 |
| SECONDARY NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) |
43.83; 8.70 | 0.8401 |
| SECONDARY Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo) |
-11.95; -0.81 | 0.0602 |
| SECONDARY Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo) |
-2.88; -8.09 | 0.2378 |
Summary
NICE is a randomized clinical trial that will examine the effects of nicotinamide riboside (NR) both with and without resveratrol to test whether, among people with PAD, NR significantly improves walking performance more than placebo and whether NR combined with resveratrol significantly improves walking performance more than placebo. If findings support the hypotheses, results will be used to design a large, definitive randomized clinical.
The study will randomize 90 participants with PAD to one of the following three groups: NR + resveratrol, NR + placebo, or placebo + placebo.
Eligibility Criteria
Inclusion Criteria
All participants will have PAD. PAD will be defined as the following: 1) An ankle-brachial index (ABI) 3.0 times the upper limit of normal. [NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.]
- Failure to successfully complete the 2-week study run-in.
- Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months.
- Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
- Participation in supervised treadmill exercise during the previous three months.
- Major medical illness including renal disease requiring dialysis, lung disease requiring oxygen, Parkinson's disease, a life-threatening illness with life expectancy less than six months, or cancer requiring treatment in the previous two years. [NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.]
- Mini-Mental Status Examination (MMSE) score <23 or dementia.
- Participation in or completion of a clinical trial in the previous three months. [NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.]
- Currently taking a dose of 250 mg or more of nicotinamide riboside, vitamin B3, niacin. Currently taking a slow-release form of niacin. Currently taking resveratrol or has taken any these drug(s) in past six months. Participants taking a multi-vitamin will not be excluded if the dose of vitamin B3 is less than 250 mgs.
- Increase in angina or angina at rest
- Non-English speaking.
- Visual impairment that limits walking ability.
- Women who are pregnant or who are pre-menopausal will not be eligible.
- In addition to the above criteria, investigator discretion will be used to determine if the trial is unsafe or not a good fit for the potential participant.
Potentially eligible participants will be advised that Medicare coverage for 12 weeks of supervised treadmill exercise is now available. Potential participants who have not participated in supervised treadmill exercise covered by Medicare and who desire to participate will be referred back to their physician for follow-up. These individuals may become eligible six months after they complete supervised treadmill exercise.
Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) and adults unable to consent will not be included in the study.
Data sourced from ClinicalTrials.gov (NCT03743636). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.