Phase 2
N=30
Nicotinamide Riboside in Systolic Heart Failure
Heart Failure, Systolic
Bottom Line
View on ClinicalTrials.gov: NCT03423342 ↗Enrolled (actual)
30
Serious AEs
10.0%
Results posted
Nov 2022
Primary outcome: Primary: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) — 3.1; 3.2 events/participant
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- nicotinamide riboside (Dietary_supplement); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Washington
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) |
3.1; 3.2 | — |
| SECONDARY On-Trial Change in Whole Blood NAD+ Levels |
29.0; -0.3 | <0.0001 sig |
| SECONDARY Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment |
0; 0 | <0.05 sig |
| SECONDARY Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate) |
21; 2 | <0.05 sig |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT03423342). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.