The NICE-PAD II Trial

Inclusion criteria

• 1. Age 50 and older.
• 2. Presence of peripheral artery disease (PAD). PAD will be defined as either: a. An ABI < 0.90 at baseline. b. Vascular lab evidence of PAD (such as a toe brachial pressure < 0.70 or an ankle brachial index less than or equal to 0.90), or angiographic evidence of PAD defined as at least 70% stenosis of an artery supplying the lower extremities. c. An ABI of >0.90 and <1.00 who experience a 20% or greater drop in ABI in either leg after the heel-rise test.

Exclusion criteria

• 1. Above- or below-knee amputation
• 2. Critical limb ischemia defined as an ABI <0.40 with symptoms of rest pain
• 3. Wheelchair confinement 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. Failure to successfully complete the study run-in
• 7. Planned major surgery, coronary or leg revascularization during the next six months
• 8. Major surgery, coronary or leg revascularization, or major cardiovascular event in the previous three months
• 9. Major medical illness including 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 require oxygen only at night may still qualify.]
• 10. Non-English speaking. The integrity of the clinical trial requires clear and effective communication for data collection and study interventions. The trial does not have sufficient staff members who are fluent in non-English languages, nor does it have the budget to translate all study materials into other languages.
• 11. Current participation in or completion of a clinical trial intervention in the previous three months. However, at investigator discretion, depending on the nature of the trial, when the intervention was administered, or whether the participant remains in long term follow-up, a potential participant formally enrolled in a clinical trial may be eligible.
• 12. Visual impairment that limits walking ability.
• 13. Participation in a supervised treadmill exercise program or in a cardiac rehabilitation program in the previous three months or who plan to begin a supervised treadmill exercise program or a cardiac rehabilitation program in the next six months.
• 14. Unstable angina.
• 15. Unwilling to participate in study intervention.
• 16. Allergy to nicotinamide riboside.
• 17. Potential participants who have taken a daily dose of 100 mg or more of nicotinamide riboside or niacin, 200 mg or more of vitamin B3, or nicotinamide mononucleotide (NMN) in the previous three months.
• 18. 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.