NCT03423342

Nicotinamide Riboside in Systolic Heart Failure

Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Aim 1: Determine the safety and tolerability of NR in patients with clinically stable, systolic heart failure (LVEF \<40%). To accomplish this Aim: A) a total of 30 participants with clinically stable, systolic heart failure (LVEF \<40%) will undergo 2:1 randomization to NR 250mg PO twice daily or matching placebo B) NR (or matching placebo), will be increased weekly by 250mg/dose (500mg/day) to a final dose of 1000mg PO twice daily. Clinic visits with labs bi-weekly during dose escalation will assess HF symptoms and monitor labs \[B-type natriuretic peptide (BNP), complete blood count (CBC), glycosylated hemoglobin, alanine aminotransferase (ALT), creatine kinase (CK), insulin/glucose, uric acid, electrolytes, blood urea nitrogen (BUN) and creatinine (Cr). C) to ensure intermediate-term safety and tolerability, participants will continue on their maximum tolerated dose (of NR or placebo) through Study Week 12 Aim 2: Determine whether, at the doses employed, NR and NAD are detectable in whole blood. Aim 3 (Exploratory): Assess the range of potential effect sizes of NR on HF surrogate endpoints using: A) Six-minute walk tests (6MWTs) at each visit (including Screening) to assess functional capacity B) Echocardiography at Baseline and Week 12 to assess LV systolic function (by real-time, 3D echocardiography) and diastolic function (by integrated Doppler and tissue Doppler imaging)

Conditions

• Heart Failure, Systolic

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	nicotinamide riboside	nicotinamide riboside capsule
DRUG	Placebo	matching placebo capsule

Timeline

• Start date: 2016-05-19
• Primary completion: 2019-04-11
• Completion: 2019-06-30
• First posted: 2018-02-06
• Last updated: 2022-11-16
• Results posted: 2022-11-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study