Nicotinamide Riboside in Systolic Heart Failure

NCT03423342 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: STUDY000018301R21HL126209-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure, Systolic

Keywords

nicotinamide riboside; Nicotinamide-Adenine Dinucleotide

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Adverse Events

  up to 12 weeks

Secondary Outcomes (3)

• On-Trial Change in Whole Blood NAD+ Levels

  Week 12-Week 0

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

  16 weeks

• Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)

  Week 12 - Week 0

Other Outcomes (3)

• Exploratory Endpoint: Effect of NR on Functional Capacity

  Week 12 - Week 0

• Exploratory Endpoint: Effect of NR on Change in Left Ventricular Systolic Function

  Week 12 - Week 0

• Exploratory Endpoint: Effect of NR on Left Ventricular Diastolic Function

  Week 12 - Week 0

Study Arms (2)

Nicotinamide Riboside

EXPERIMENTAL

Nicotinamide riboside will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12.

Dietary Supplement: nicotinamide riboside

Placebo

PLACEBO COMPARATOR

Matching placebo will be supplied as 250mg capsules, to be administered orally. The initial dose will be 1 capsule twice daily, followed by weekly up-titration by 1 capsule/dose to a final dose of 4 capsules (1000mg) twice daily at the end of Week 4. Participants will be continued on the final dose up to the final follow up visit (week 12). If, at any step, a dose increase is not tolerated, the maximum previously-tolerated dose will be continued through to week 12.

Drug: Placebo

Interventions

nicotinamide riboside DIETARY_SUPPLEMENT

nicotinamide riboside capsule

Also known as: Niagen

Nicotinamide Riboside

Placebo DRUG

matching placebo capsule

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Wang DD, Airhart SE, Zhou B, Shireman LM, Jiang S, Melendez Rodriguez C, Kirkpatrick JN, Shen DD, Tian R, O'Brien KD. Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. JACC Basic Transl Sci. 2022 Sep 14;7(12):1183-1196. doi: 10.1016/j.jacbts.2022.06.012. eCollection 2022 Dec.

  PMID: 36644285 DERIVED

MeSH Terms

Conditions

Heart Failure, Systolic

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Kevin O'Brien, Study PI
• Organization: University of Washington

cardiac@uw.edu

206-529-7802

Study Officials

• Kevin D O'Brien, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization and dispensing of matching placebo will be performed by Investigational Drug Services at the University of Washington
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine/Cardiology

Model Details: 2:1 randomization to nicotinamide riboside vs. matching placebo

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: February 6, 2018
• Study Start: May 19, 2016
• Primary Completion: April 11, 2019
• Study Completion: June 30, 2019
• Last Updated: November 16, 2022
• Results First Posted: November 16, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 2 years following Study completion

Locations

US (1)