Primary outcomeMean· up to 12 weeks
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
| Group | Value (events/participant) |
|---|---|
| Nicotinamide Riboside | 3.1 |
| Placebo | 3.2 |
Trial · Interventional
CompletedPhase 1/2Results postedRegistry dataNicotinamide Riboside in Systolic Heart Failure
This trial does not test a peptide that PepBank tracks.
- Measures NAD+ (nicotinamide adenine dinucleotide), does not give it. It appears in an outcome measure.
Overview
- Status
- Completed
- Phase
- Phase 1/2
- Enrollment
- 30 participants (actual)
- Sponsor
- University of Washington · Other
- Design
- Randomized · Triple masking
- Countries
1 country
United States
- Start
- 19 May 2016
- Primary completion
- 11 Apr 2019
- Completion
- 30 Jun 2019
- First posted
- 6 Feb 2018
- Last update posted
- 16 Nov 2022
- Conditions
- Heart Failure, Systolic
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20162017201820192020
- Ph 1/2
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- nicotinamide ribosideDietary supplement
- PlaceboDrug
Arms2
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.
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.
Primary outcomes1
Outcomes the sponsor listed as primary.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame · up to 12 weeks
Registry description
Adverse Events
Secondary outcomes(3)
On-Trial Change in Whole Blood NAD+ Levels
Time frame · Week 12-Week 0
Registry description
Between-group comparison of On-Trial Change in Whole Blood NAD+ Levels
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time frame · 16 weeks
Registry description
Incidence of On-Trial Abnormal Laboratory Values and/or Adverse Events that Are Related to Treatment
Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)
Time frame · Week 12 - Week 0
Registry description
Mitochondrial Respiration in Isolated Peripheral Blood Mononuclear Cells by the Seahorse (R) Assay
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(6)
Secondary outcomeMean· Week 12-Week 0
On-Trial Change in Whole Blood NAD+ Levels
| Group | Value (uM) | Spread |
|---|---|---|
| Nicotinamide Riboside | 29.0 | 3.2 |
| Placebo | -0.3 | 0.6 |
Secondary outcomeNumber· 16 weeks
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
| Group | Value (participants) |
|---|---|
| Nicotinamide Riboside | 0 |
| Placebo | 0 |
Secondary outcomeMean· Week 12 - Week 0
Effect of NR on Change in Mitochondrial Function (Maximal Oxygen Consumption Rate)
| Group | Value (pmol/min/1,000,000 cells) | Spread |
|---|---|---|
| Nicotinamide Riboside | 21 | 42 |
| Placebo | 2 | 23 |
Other pre specified outcomeMean· Week 12 - Week 0
Exploratory Endpoint: Effect of NR on Functional Capacity
| Group | Value (meters) | Spread |
|---|---|---|
| Nicotinamide Riboside | 6 | 8 |
| Placebo | 1 | 15 |
Other pre specified outcomeMean· Week 12 - Week 0
Exploratory Endpoint: Effect of NR on Change in Left Ventricular Systolic Function
| Group | Value (percentage of ejection fraction) | Spread |
|---|---|---|
| Nicotinamide Riboside | 0.0 | 2.2 |
| Placebo | 0.3 | 2.2 |
Other pre specified outcomeMean· Week 12 - Week 0
Exploratory Endpoint: Effect of NR on Left Ventricular Diastolic Function
| Group | Value (cm/sec) | Spread |
|---|---|---|
| Nicotinamide Riboside | 0.37 | 0.54 |
| Placebo | -0.44 | 0.39 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Nicotinamide RibosideNicotinamide 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. nicotinamide riboside: nicotinamide riboside capsule | 0 / 20 | 1 / 20 | 19 / 20 |
| PlaceboMatching 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. Placebo: matching placebo capsule | 0 / 10 | 2 / 10 | 9 / 10 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- DerivedWang 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
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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
PepBank is a research reference. Talk to a doctor before you use any peptide.