Clinical trial NCT03743636: Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease
Official title: Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease: The NICE Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Peripheral Artery Disease
Keywords: Peripheral Artery Disease
PAD
Resveratrol
Nicotinamide riboside (NR)
Six-minute walk
Functional performance
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2018-11-16
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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) \<=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.

Primary outcomes:
measure: Six-minute Walk Distance (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
Secondary outcomes:
measure: Six-minute Walk Distance (NR Alone vs. Placebo)
timeFrame: Baseline to 3-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 3-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 3-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Maximal Treadmill Walking Time (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Distance Score (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Maximal Treadmill Walking Time (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Maximal Treadmill Walking Time (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 3-month follow-up
measure: Six-minute Walk Distance (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Maximal Treadmill Walking Time (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Distance Score (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Physical Activity (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Satellite Cell Abundance in Gastrocnemius Muscle (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Gastrocnemius Muscle Fiber Phenotype(NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
Other outcomes:
measure: Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Speed Score (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Short-Form Physical Functioning (SF-36) Score (NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Stair Climbing Score (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol vs. NR Alone)
timeFrame: Baseline to 6-month follow-up
measure: Walking Impairment Questionnaire (WIQ) Speed Score (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
measure: Short-Form Physical Functioning (SF-36) Score (NR/Resveratrol or NR Alone vs. Placebo)
timeFrame: Baseline to 6-month follow-up
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Mary M McDermott, MD
role: PRINCIPAL_INVESTIGATOR
References: