Nicotinamide Riboside in Systolic Heart Failure
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ClinicalTrials.gov Identifier: NCT03423342 |
Recruitment Status
:
Recruiting
First Posted
: February 6, 2018
Last Update Posted
: February 6, 2018
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Condition or disease | Intervention/treatment | Phase |
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Heart Failure, Systolic | Dietary Supplement: nicotinamide riboside Drug: Placebo | Phase 1 Phase 2 |
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)
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 30 participants |
Allocation: | Randomized |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | 2:1 randomization to nicotinamide riboside vs. matching placebo |
Masking: | Triple (Participant, Care Provider, Investigator) |
Masking Description: | Randomization and dispensing of matching placebo will be performed by Investigational Drug Services at the University of Washington |
Primary Purpose: | Other |
Official Title: | Safety and Tolerability of the Nutritional Supplement, Nicotinamide Riboside, in Systolic Heart Failure |
Actual Study Start Date : | May 19, 2016 |
Estimated Primary Completion Date : | May 1, 2018 |
Estimated Study Completion Date : | June 30, 2018 |
Arm | Intervention/treatment |
---|---|
Experimental: Nicotinamide Riboside
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.
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Dietary Supplement: nicotinamide riboside |
Placebo Comparator: Placebo
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.
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Drug: Placebo |
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: up to 12 weeks ]Adverse Events
- Effect of NR on Whole Blood NAD+ Levels [ Time Frame: Week 12 ]Between-group comparison of Whole Blood NAD+ Levels at Week 12
- Number of Participants with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: up to 12 weeks ]Incidence of On-Trial Abnormal Laboratory Values and/or Adverse Events that Are Related to Treatment
- Effect of NR on Mitochondrial Function [ Time Frame: Week 12 ]Mitochondrial Respiration in Isolated Peripheral Blood Mononuclear Cells by the Seahorse (R) Assay
- Exploratory Endpoint: Effect of NR on Functional Capacity [ Time Frame: Clinic Visits at Weeks -2 (Screening), 0 (Baseline), 2, 4, 8 and 12 (Final) ]Six Minute Walk Test
- Exploratory Endpoint: Effect of NR on Left Ventricular Systolic Function [ Time Frame: Clinic Visits at Weeks 0 (Baseline) and 12 (Final) ]Left Ventricular Ejection Fraction by 3D-Transthoracic Echocardiography
- Exploratory Endpoint: Effect of NR on Left Ventricular Diastolic Function [ Time Frame: Clinic Visits at Weeks 0 (Baseline) and 12 (Final) ]Tissue Doppler Imaging

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03423342
Contact: Kevin D O'Brien, MD | 206 685-3930 | cardiac@uw.edu | |
Contact: Rong Tian, MD | 206 616-5672 | rongtian@u.washington.edu |
United States, Washington | |
University of Washington | Recruiting |
Seattle, Washington, United States, 98195 | |
Contact: Kevin D O'Brien, MD 206-529-7802 cardiac@uw.edu | |
Contact: Rong Tian, MD 206 616-5672 rongtian@u.washington.edu |
Principal Investigator: | Kevin D O'Brien, MD | University of Washington |
Documents provided by Kevin O'Brien, University of Washington:
Responsible Party: | Kevin O'Brien, Professor, Medicine/Cardiology, University of Washington |
ClinicalTrials.gov Identifier: | NCT03423342 History of Changes |
Other Study ID Numbers: |
STUDY00001830 1R21HL126209-01 ( U.S. NIH Grant/Contract ) |
First Posted: | February 6, 2018 Key Record Dates |
Last Update Posted: | February 6, 2018 |
Last Verified: | January 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | A de-identified, public access database will be made available two years after publication of the primary study results. Data files will be delivered in electronic format, providing meta-data that completely describes the tables, variables and coding. Both the raw data and the primary analysis files will be included. Primary analysis files are a compilation of key variables used to generate the statistical results, to help assure that investigators reach consistent conclusions when analyzing the data to published results. Data, documentation and all other materials will be delivered to NHLBI, as well as a document that fully describes the data, steps taken to de-identify the data, and quality control procedures. A document summarizing data tables and other files that are being delivered and describing the data manipulations applied to the data to assure data anonymity, including an annotated clinical study report providing the database variable names. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code |
Time Frame: | 2 years following Study completion |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No | |
Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by Kevin O'Brien, University of Washington:
nicotinamide riboside Nicotinamide-Adenine Dinucleotide |
Additional relevant MeSH terms:
Niacinamide Niacin Nicotinic Acids Heart Failure Heart Failure, Systolic Heart Diseases Cardiovascular Diseases Vitamin B Complex Vitamins |
Micronutrients Growth Substances Physiological Effects of Drugs Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Vasodilator Agents |