Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease (NICE)

Northwestern University

Status and phase: Completed; Phase 3

Conditions: Peripheral Artery Disease

Treatments: Drug: Nicotinamide riboside; Other: Placebo; Drug: Resveratrol

Study type: Interventional

Funder types: Other

Identifiers

NCT03743636

STU00206660

Details and patient eligibility

About

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.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

All participants will have PAD. PAD will be defined as the following: 1) An ankle-brachial index (ABI) <=0.90 at the baseline study visit or 2) Vascular laboratory evidence or angiographic evidence of PAD. Inclusion based on prior vascular laboratory evidence will be determined by the study principal investigator and includes, for example, a toe brachial index (TBI) < 0.70, Duplex measure showing 70% stenosis or great, a post heel-rise or post-exercise ABI drop of 20% or greater, or ABI values <= 0.90. Angiographic evidence of PAD consists of a stenosis of 70% or greater in a lower extremity artery.

Exclusion criteria

1. Above- or below-knee amputation.
2. Critical limb ischemia.
3. Wheelchair-bound or requiring a walker to ambulate.
4. Walking is limited by a symptom other than PAD.
5. Current foot ulcer on bottom of foot.
6. End stage renal disease defined as a GFR less than 20 ml/min/1.73 M2.
7. Significant liver impairment defined as two or more hepatic function enzymes >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.]
8. Failure to successfully complete the 2-week study run-in.
9. Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months.
10. Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
11. Participation in supervised treadmill exercise during the previous three months.
12. 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.]
13. Mini-Mental Status Examination (MMSE) score <23 or dementia.
14. 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.]
15. 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.
16. Increase in angina or angina at rest
17. Non-English speaking.
18. Visual impairment that limits walking ability.
19. Women who are pregnant or who are pre-menopausal will not be eligible.
20. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 3 patient groups, including a placebo group

Nicotinamide riboside + resveratrol

Active Comparator group

Description:

Participants randomized to the NR + resveratrol arm of the study will receive 1,000 mg of NR and 125 mg of resveratrol daily for six months.

Treatment:

Drug: Resveratrol

Drug: Nicotinamide riboside

Nicotinamide riboside + placebo

Active Comparator group

Description:

Participants randomized to the NR + placebo arm of the study will receive 1,000 mg of NR and a placebo daily for six months.

Treatment:

Other: Placebo

Drug: Nicotinamide riboside

Placebo + placebo

Placebo Comparator group

Description:

Participants randomized to the placebo + placebo arm of study will receive placebo pills.

Treatment:

Other: Placebo