Nicotinamide Riboside in Systolic Heart Failure

• Status: Completed
• Trial end date: 2019-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Mitochondrial dysfunction has been implicated in heart failure (HF), and is associated with an imbalance in intracellular ratio of reduced nicotinamide-adenine dinucleotide (NADH) to oxidized nicotinamide-adenine dinucleotide (NAD), or the NADH/NAD ratio. In mouse models of HF, we have found that normalization of the NADH/NAD, through supplementation with NAD+ precursors, is associated with improvement in cardiac function. This Study will randomize participants with systolic HF (ejection fraction ≤40%) to treatment with the NAD precursor, nicotinamide riboside (NR) or matching placebo, uptitrated to a final oral dose of 1000mg twice daily, to determine the safety and tolerability of NR in participants with systolic HF.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Niacin; Niacinamide; Nicotinic Acids

Criteria

Inclusion Criteria:

• Men and women aged 18 and older with systolic heart failure [left ventricular ejection fraction (LVEF) by standard 2D echocardiography or radionuclide ventriculography of ≤40%] deemed, in the clinical opinion of their treating cardiologist 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 and six-minute walk test (6MWT)

• Willingness/ability to provide informed consent

Exclusion Criteria:

• Heart failure with preserved ejection fraction (LVEF greater than 40%)

• Heart failure due, in the opinion of their treating cardiologist, to etiologies other than non-ischemic or ischemic. Examples of exclusionary heart failure etiologies include primary valvular disease, or infiltrative or inflammatory cardiomyopathies.

• 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, transient ischemic attack or arrhythmias within the previous 3 months

• Inability to perform Study visits or procedures (e.g., physical inability to perform 6MWT)

• Unwillingness/inability to provide informed consent

• ALT greater than 3 times the upper limit of normal, hepatic insufficiency or active liver disease

• Recent history of acute gout

• Chronic renal insufficiency with creatinine ≥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 long-term clinical trial

• History of intolerance to NR precursor compounds, including niacin or nicotinamide