Mechanistic Studies of Nicotinamide Riboside in Human Heart Failure

• Status: Recruiting
• Trial end date: 2024-08-31
• Target enrollment: 0
• Participant gender: All

Summary

Preliminary animal studies by ourselves and others suggest that the dietary supplement, nicotinamide riboside (NR), may improve cardiac function in heart failure (HF) by increasing cellular levels of its metabolite, nicotinamide adenine dinucleotide (NAD+, NADH). This Study will address a key gap in current knowledge by assessing the mechanisms through which raising blood and myocardial NAD+ levels in humans mediates changes in mitochondrial function, protein and epigenetic modifications, as well as inflammation. Human myocardium will be obtained after 4-14 days of oral NR supplementation from advanced heart failure patients undergoing elective left ventricular assist device (LVAD) implantation. Positive results would provide evidence to proceed with further studies of NR as a mitochondria-targeted metabolic therapy in heart failure.

• Phase: Early Phase 1
• 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:

1. End-stage heart failure due to ischemic or non-ischemic cardiomyopathy

a. If implanted for destination therapy indication, must have New Your Heart Association (NYHA) Class IV Heart Failure AND left ventricular ejection fraction (LVEF) <25% OR maximum minute consumption of oxygen (VO2) <14 OR on requirement for continuous intravenous inotropes

2. Meet clinical and socioeconomic screening criteria for elective LVAD implantation by the University of Washington Mechanical Circulatory Support Program

3. Scheduled (or soon to be scheduled) for elective LVAD implantation

4. Age >18 years

Exclusion Criteria:

1. End-stage heart failure due to causes other than ischemic or non-ischemic cardiomyopathy (e.g., valvular, hypertrophic or infiltrative cardiomyopathies).

2. Disease that disqualifies from consideration for LVAD implantation by the University of Washington program:

1. Cirrhosis as evidenced by liver biopsy

2. Irreversible, severe renal disease (estimated glomerular filtration rate (eGFR) <30) or on chronic dialysis

3. Untreated thyroid disease (hyper- or hypo-thyroidism)

4. Severe complications of diabetes, such as diabetes-related amputation, severe retinopathy, peripheral neuropathy or diabetic renal disease (eGFR <30)

3. Tissue physiology or other factors that, in the opinion of the Cardiac Surgeons, make the patient at unacceptably high risk for adverse outcomes.

4. Non-compliance with current treatments, including failure to follow prescribed therapies, such as medications, clinic visits, diagnostic testing and behavioral contracts

5. Active use/abuse of illicit substances

6. Lack of adequate caregiver support to help patient manage LVAD

7. Known allergies to niacin, nicotinamide or warfarin

8. Inability to perform Study visits or procedures

9. Unwillingness/inability to provide informed consent.

10. Participants considered by the attending cardiologist and/or the investigator to be unsuitable for the study