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

NCT03743636 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: STU00206660
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral Artery Disease

Keywords

Peripheral Artery Disease; PAD; Resveratrol; Nicotinamide riboside (NR); Six-minute walk; Functional performance

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (21)

• Six-minute Walk Distance (NR Alone vs. Placebo)

  Baseline to 3-month follow-up

• Six-minute Walk Distance (NR/Resveratrol vs. Placebo)

  Baseline to 3-month follow-up

• Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)

  Baseline to 3-month follow-up

• Six-minute Walk Distance (NR/Resveratrol vs. NR Alone)

  Baseline to 6-month follow-up

• Maximal Treadmill Walking Time (NR Alone vs. Placebo)

  Baseline to 6-month follow-up

Other Outcomes (11)

• Gastrocnemius Muscle Satellite Cell Abundance (NR/Resveratrol vs. Placebo and NR vs. Placebo)

  Baseline to 6-month follow-up

• NAD+ Abundance in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)

  Baseline to 6-month follow-up

• Muscle Fiber Phenotype in Gastrocnemius Muscle (NR/Resveratrol vs. Placebo and NR vs. Placebo)

  Baseline to 6-month follow-up

Study Arms (3)

Nicotinamide riboside + resveratrol

ACTIVE COMPARATOR

Participants randomized to the NR + resveratrol arm of the study will receive 1,000 mg of NR and 125 mg of resveratrol daily for six months.

Drug: Nicotinamide riboside; Drug: Resveratrol

Nicotinamide riboside + placebo

ACTIVE COMPARATOR

Participants randomized to the NR + placebo arm of the study will receive 1,000 mg of NR and a placebo daily for six months.

Drug: Nicotinamide riboside; Other: Placebo

Placebo + placebo

PLACEBO COMPARATOR

Participants randomized to the placebo + placebo arm of study will receive placebo pills.

Other: Placebo

Interventions

Nicotinamide riboside DRUG

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.

Also known as: NR, Niagen

Nicotinamide riboside + placebo; Nicotinamide riboside + resveratrol

Resveratrol DRUG

Participants randomized to the NR + resveratrol arm of the study will receive 125 mg of resveratrol daily for six months.

Nicotinamide riboside + resveratrol

Placebo OTHER

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.

Nicotinamide riboside + placebo; Placebo + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Above- or below-knee amputation.
• Critical limb ischemia.
• Wheelchair-bound or requiring a walker to ambulate.
• Walking is limited by a symptom other than PAD.
• Current foot ulcer on bottom of foot.
• End stage renal disease defined as a GFR less than 20 ml/min/1.73 M2.
• Significant liver impairment defined as two or more hepatic function enzymes \>3.0 times the upper limit of normal. \[NOTE: participants who meet this criterion may undergo a re-test of hepatic function tests to determine whether initially elevated hepatic enzymes represented a transient or spurious phenomenon.\]
• Failure to successfully complete the 2-week study run-in.
• Planned lower extremity revascularization, orthopedic surgery, or other major surgery during the next six months.
• Lower extremity revascularization, orthopedic surgery, cardiovascular event, coronary revascularization, or other major surgery in the previous three months.
• Participation in supervised treadmill exercise during the previous three months.
• 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. \[NOTE: potential participants may still qualify if they have had treatment for an early stage cancer in the past two years and the prognosis is excellent. Participants who only use oxygen at night may still qualify.\]
• Mini-Mental Status Examination (MMSE) score \<23 or dementia.
• Participation in or completion of a clinical trial in the previous three months. \[NOTE: after completing a stem cell or gene therapy intervention, participants will become eligible after the final study follow-up visit of the stem cell or gene therapy study so long as at least six months have passed since the final intervention administration. After completing a supplement or drug therapy (other than stem cell or gene therapy), participants will be eligible after the final study follow-up visit as long as at least three months have passed since the final intervention of the trial.\]
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• American Heart Association: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Nayak P, Polonsky T, Tian L, Greenland P, Xu S, Zhang D, Zhao L, Criqui MH, Kibbe MR, Gladders B, Goodney P, Ho K, Guralnik JM, McDermott MM. Medical therapies, comorbid conditions, and functional performance in people with peripheral artery disease enrolled in clinical trials between 2004 and 2021. Vasc Med. 2023 Apr;28(2):144-146. doi: 10.1177/1358863X221145533. Epub 2023 Jan 1.

  PMID: 36588397 DERIVED

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

nicotinamide-beta-riboside; Resveratrol

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Results Point of Contact

• Title: Mary M. McDermott, MD
• Organization: Northwestern University

mdm608@northwestern.edu

312-503-6419

Study Officials

• Mary M McDermott, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine at Northwestern University Feinberg School of Medicine

Study Record Dates

• First Submitted: May 20, 2018
• First Posted: November 16, 2018
• Study Start: October 1, 2018
• Primary Completion: May 23, 2023
• Study Completion: May 23, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)