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

Inclusion Criteria:

All participants will have PAD. PAD will be defined as an ankle-brachial index (ABI) <0.90
at the baseline study visit.

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 study drug(s) or has taken study drug(s) in past six months.

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.