The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects

NCT03565328 | Terminated Phase 2 Results

• 2 other identifiers: 18010718-H-0107
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

Background: People are living longer and are more likely to survive a heart attack if they have one. Longer life expectancy is good but it also means more people get chronic heart failure over time. This is a condition in which the heart doesn't pump blood as well as it should. Treatment of chronic heart failure has not improved much in a few decades. Researchers want to see if giving a dietary supplement to people with heart failure can help their heart function. The supplement is nicotinamide riboside (NR). Objective: To study how NR affects skeletal muscle function in people with heart failure. Eligibility: Adults ages 18-70 with clinically stable systolic heart failure Design: Participants will be screened with a medical history and physical exam. They will answer demographic questions and review their current medical treatments. They will have blood and urine tests. They will have an echocardiogram. This uses sound waves to test heart function. Participants will have 8 study visits over 16 weeks. At these visits, they will have some of the following: Repeat of screening tests Skin sample taken Skeletal muscle exercise Nuclear magnetic resonance (NMR) spectroscopy. Muscles will be measured while participants do foot exercises. Cardiopulmonary exercise testing. Participants may ride a stationary bike or walk on a treadmill. A facemask will analyze their breath. Heart and blood pressure measurements will be taken. Participants will take the supplement in pill form each day for 12 weeks. Pill bottles will be checked at study visits. Participants should not significantly change their activity levels during the study.

Conditions

Heart Failure

Keywords

Mitochondrial bioenergetic dysfunction; Mitochondrial oxidative phosphorylation in skeletal muscles; Hyperacetylation of mitochondrial bioenergetic enzymes; NAD+ dependent sirtuin enzymes; NAD+/NADH ratio

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Had Enhancement of Mitochondrial Function in Skeletal Muscle

  Number of participants who had enhancement mitochondrial function in skeletal muscle Nuclear magnetic resonance (NMR) spectroscopy will be performed at baseline, at the end of the 12-week Nicotinamide Riboside (NR) supplementation period and repeated 4 weeks post-NR washout.

  baseline-12 week-16 week

Secondary Outcomes (4)

• Measure the Effects of Nicotinamide Riboside (NR) on Oxidative Phosphorylation and Inflammation in Respective Subject Primary Skin Fibroblasts

  Baseline, 12 week

• Number of Participants Without Heart Failure Linked Inflammation

  Baseline, 12 week

• Number of Participants Who Experienced an Increased Rate of Oxidative Phosphorylation

  Baseline, 12 week

• VO2 Max and Anaerobic Thresholds

  Baseline, 12 week

Study Arms (1)

Nicotinamide Riboside in patients with stable heart failure

EXPERIMENTAL

Nicotinamide Riboside (NR) will be started at 500 mg daily (250 mg BID) then increased at two weekly intervals by 250 mg/dose (BID) (500 mg/day) to a final dose of 1000 mg PO BID (2000 mg/day) in patients with stable, systolic heart failure.

Dietary Supplement: Nicotinamide Riboside

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

Nicotinamide Riboside (NR) will be started at 500 mg daily (250 mg BID) be increased at two weekly intervals by 250 mg/dose (BID) (500 mg/day) to a final dose of 1000mg PO BID (2000 mg/day).

Also known as: Niagen; Nicotinamide Riboside (NR)

Nicotinamide Riboside in patients with stable heart failure

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of 18 and 75 years with New York Heart Association (NYHA) Functional Classification Class II-III systolic heart failure ( Left Ventricular Ejection Fraction (LVEF) by standard echocardiography or radionuclide ventriculography of less than or equal to 45%) deemed to be non-ischemic or ischemic in origin.
• Clinically stable (no cardiac procedures or hospitalizations for hospitalizations for cardiac causes, including HF, ischemia or arrhythmia) within the previous 3 months
• Ability to undergo study procedures, including scheduled visits, blood draws, skeletal muscle exercise NMR spectroscopy and CPET testing
• Willingness/ability to provide informed consent
• Must be DEERS eligible to be enrolled in a research protocol at Walter Reed National Military Medical Center (WRNMMC).

You may not qualify if:

• Heart failure with preserved ejection fraction (LVEF greater than 45%)
• Change in heart failure medications due to deterioration of function with the exception of up- or down-titration of diuretic dose up to 100% of baseline dose.
• Cardiac surgery, percutaneous coronary intervention (PCI) or cardiac device implantation within the previous 3 months
• Hospitalizations for cardiovascular causes, including heart failure, chest pain, stroke/TIA or arrhythmias within the previous 3 months
• Inability to perform Study visits or procedures (e.g., physical inability to perform exercise testing)
• Unwillingness/inability to provide informed consent
• ALT greater than x3 upper limit of normal, hepatic insufficiency or active liver disease
• Recent history of acute gout
• Chronic renal insufficiency with creatinine greater than 2.5mg/dl
• Pregnant (or likely to become pregnant) women
• Significant co-morbidity likely to cause death in the 6 month follow-up period
• Significant active history of substance abuse within the previous 5 years
• Current participation in another drug study
• History of intolerance to NR precursor compounds, including niacin or nicotinamide
• MRI incompatible hardware including pacemakers or ICD s

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Michael Sack, M.D. Principal Investigator, NIH, NHLBI
• Organization: National Heart Lung and Blood Institute (NHLBI)

sackm@nhlbi.nih.gov

301.402.9259

Study Officials

• Michael N Sack, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: June 21, 2018
• Study Start: September 27, 2018
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: October 28, 2020
• Results First Posted: October 28, 2020

Record last verified: 2019-11

Locations

US (2)