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

Peripheral Artery Disease Clinical Trial

— NICE  

Official title:

Nicotinamide Riboside With and Without Resveratrol to Improve Functioning in Peripheral Artery Disease: The NICE Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03743636
• Other study ID #: STU00206660
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2018
• Est. completion date: May 23, 2023

Study information

• Verified date: June 2023
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: May 23, 2023
• Est. primary completion date: May 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Artery Disease

Intervention

Drug:
• Nicotinamide riboside
Participants randomized to the NR + resveratrol arm or the NR + placebo arm of the study will receive 1,000 mg of NR daily for six months.
• Resveratrol
Participants randomized to the NR + resveratrol arm of the study will receive 125 mg of resveratrol daily for six months.

Other:
• Placebo
Participants randomized to the NR + placebo arm of the study will receiving placebo pills that are identical in appearance to resveratrol. Participants randomized to the placebo + placebo arm of the study will receive pills that are identical in appearance to NR and resveratrol. Participants will receive placebo pills daily for six months.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	American Heart Association

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gastrocnemius muscle satellite cell abundance (NR/resveratrol vs. placebo and NR vs. placebo)	Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased satellite cell abundance compared to the placebo group.	Baseline to 6-month follow-up
Other	NAD+ abundance in gastrocnemius muscle (NR/Resveratrol vs. placebo and NR vs. placebo)	Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have increased calf muscle NAD+ abundance, compared to the placebo group.	Baseline to 6-month follow-up
Other	Muscle fiber phenotype in gastrocnemius muscle (NR/Resveratrol vs. placebo and NR vs. placebo)	Investigators will perform calf muscle biopsies to determine whether among participants with PAD, those randomized to NR + resveratrol and NR alone have improved muscle fiber phenotype, compared to the placebo group.	Baseline to 6-month follow-up
Other	Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves the WIQ speed and stair climbing score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Other	Short-Form Physical Functioning (SF-36) score (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves the WIQ speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Other	Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the WIQ speed and stair climbing scores at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Other	Short-Form Physical Functioning (SF-36) score (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Other	Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the WIQ speed and stair climbing score at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Other	Short-Form Physical Functioning (SF-36) score (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the WIQ speed and stair climbing scores and the Short-Form Physical Functioning score at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Other	Walking Impairment Questionnaire (WIQ) speed and stair climbing score (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Walking Impairment Questionnaire (WIQ) speed and stair climbing score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Other	Short-Form Physical Functioning (SF-36) score (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group) have greater improvement in the Short-Form Physical Functioning score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Primary	Six-minute walk distance (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves six-minute walk distance at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Primary	Six-minute walk distance (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Six-minute walk distance (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves six-minute walk performance at 3-month follow-up, compared to placebo.	Baseline to 3-month follow-up
Secondary	Six-minute walk distance (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to placebo.	Baseline to 3-month follow-up
Secondary	Six-minute walk distance (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 3-month follow-up, compared to NR alone.	Baseline to 3-month follow-up
Secondary	Six-minute walk distance (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves six-minute walk performance at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Secondary	Maximal treadmill walking time (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves maximal treadmill walking time at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Walking Impairment Questionnaire (WIQ) distance score (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves the WIQ distance score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Physical activity (NR alone vs. placebo)	Among participants with PAD, investigators will determine whether NR alone improves physical activity at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Maximal treadmill walking time (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the WIQ distance score at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Physical activity (NR/Resveratrol vs. placebo)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to placebo.	Baseline to 6-month follow-up
Secondary	Maximal treadmill walking time (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves maximal treadmill walking time at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Secondary	Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves the Walking Impairment Questionnaire (WIQ) distance score at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Secondary	Physical activity (NR/Resveratrol vs. NR alone)	Among participants with PAD, investigators will determine whether NR combined with resveratrol improves physical activity at 6-month follow-up, compared to NR alone.	Baseline to 6-month follow-up
Secondary	Six-minute walk distance (NR/Resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo.	Baseline to 3-month follow-up
Secondary	Six-minute walk distance (NR/Resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in six-minute walk distance, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	Maximal treadmill walking time (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in maximal treadmill walking time, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	Walking Impairment Questionnaire (WIQ) distance score (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in WIQ distance score, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	Physical Activity (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in physical activity, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	NAD+ Abundance in gastrocnemius muscle (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in NAD+ abundance, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	Satellite Cell Abundance in gastrocnemius muscle (NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in satellite cell abundance, compared to those randomized to placebo.	Baseline to 6-month follow-up
Secondary	Gastrocnemius Muscle Fiber Phenotype(NR/resveratrol or NR alone vs. placebo)	Participants with PAD who received NR alone and those who received NR + resveratrol will be combined into one group and compared to the group receiving placebo, to determine whether NR alone or NR+ resveratrol (combined group)have greater improvement in muscle fiber phenotype, compared to those randomized to placebo.	Baseline to 6-month follow-up