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

• Status: Recruiting
• Trial end date: 2022-04-01
• Target enrollment: 0
• Participant gender: All

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 our findings support our hypotheses, results will be used to design a large, definitive randomized clinical.

We will randomize 90 participants with PAD to one of the following three groups: NR + resveratrol, NR + placebo, or placebo + placebo. Our primary outcome is change in six-minute walk distance between baseline and 6-month follow-up. Secondary outcomes are change in maximal treadmill walking time, patient-reported walking ability (measured by the Walking Impairment Questionnaire (WIQ)), quality of life (measured by the Short Form-36 Physical Functioning (SF-36 PF) score), and physical activity (measured by accelerometer). Calf skeletal muscle biopsy specimens collected in participants in the NICE Trial will be analyzed for NAD+ abundance, stem cell (satellite cell) abundance and muscle fiber phenotype.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Collaborator: American Heart Association
• Treatments: Niacin; Niacinamide; Nicotinic Acids; Resveratrol

Criteria

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 nicotinomide 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.