Nicotinamide Riboside for Heart Failure
(NRII Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Waitlist Available
Sponsor: University of Washington
Disqualifiers: Cirrhosis, Severe renal disease, Untreated thyroid, others
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial tests whether a vitamin B3 supplement called nicotinamide riboside can help patients with severe heart failure by improving their cell energy production and reducing inflammation. The study focuses on patients undergoing heart surgery to implant a device that helps their heart pump blood.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, it mentions that non-compliance with current treatments is an exclusion criterion, suggesting that you may need to continue your existing medications.
How is the drug Nicotinamide Riboside unique in treating heart failure?
Eligibility Criteria
This trial is for adults over 18 with advanced heart failure who are scheduled for a left ventricular assist device (LVAD) implant. They must have severe symptoms or low heart function, and meet specific health criteria. People with other types of heart failure, serious liver or kidney disease, untreated thyroid issues, severe diabetes complications, high surgical risk factors, non-compliance to treatments, substance abuse problems or lack of caregiver support cannot join.Inclusion Criteria
I have advanced heart failure from a heart muscle problem.
Meet clinical and socioeconomic screening criteria for elective LVAD implantation by the University of Washington Mechanical Circulatory Support Program
I have severe heart failure with very poor heart function or need constant heart medication.
See 2 more
Exclusion Criteria
You have liver disease, severe kidney problems, untreated thyroid issues, severe complications from diabetes, or other health issues that make it too risky for you to have a heart pump implanted. You also must follow your doctor's orders and not abuse drugs or have problems getting to your medical appointments.
My heart failure is not caused by common heart muscle issues.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive nicotinamide riboside (NR) or placebo with dose escalation over 3 days, followed by maintenance dosing until the day before LVAD surgery
14 days
Daily dosing with final labs on the day of surgery
Follow-up
Participants are monitored for safety and effectiveness after treatment, including analysis of myocardial and blood samples
4 weeks
Treatment Details
Interventions
- Nicotinamide Riboside (Vitamin)
Trial OverviewThe study tests if nicotinamide riboside (NR), a dietary supplement thought to improve cardiac function by boosting NAD+ levels in the body can help patients with heart failure. Participants will take NR orally before getting an LVAD implantation to see if it improves mitochondrial function and reduces inflammation compared to a placebo.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Nicotinamide ribosideExperimental Treatment1 Intervention
Participants randomized to Nicotinamide Riboside (NR) and scheduled to receive an LVAD will receive nicotinamide riboside (NR) capsules according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg) Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily Washout Day of LVAD Surgery and/or Day 15: None
Group II: PlaceboPlacebo Group1 Intervention
Participants randomized to Placebo and scheduled to receive an LVAD will receive Placebo capsules according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg) Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily Washout Day of LVAD Surgery and/or Day 15: None
Nicotinamide Riboside is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Niagen for:
- Dietary supplement for general health and wellness
🇪🇺 Approved in European Union as Niagen for:
- Dietary supplement for general health and wellness
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of WashingtonSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction. [2023]Label="AIMS" NlmCategory="OBJECTIVE">Myocardial infarction (MI) is a major cause of death. Nicotinamide adenine dinucleotide (NAD+) is a coenzyme in oxidative phosphorylation and substrate of sirtuins and poly-ADP ribose polymerases, enzymes critical for cardiac remodeling post-MI. Decreased NAD+ is reported in several heart failure models with paradoxically an upregulation of nicotinamide riboside kinase 2, which uses nicotinamide riboside (NR) as substrate in an NAD+ biosynthetic pathway. We hypothesized that stimulating nicotinamide riboside kinase 2 pathway by NR supplementation exerts cardioprotective effects.
Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. [2023]The mitochondrial dysfunction characteristic of heart failure (HF) is associated with changes in intracellular nicotinamide adenine dinucleotide (NAD+) and NADH levels. Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment. In this 30-participant trial of patients with clinically stable HF with reduced ejection fraction, NR, at a dose of 1,000 mg twice daily, appeared to be safe and well tolerated, and approximately doubled whole blood NAD+ levels. Intraindividual NAD+ increases in response to NR correlated with increases in peripheral blood mononuclear cell basal (R 2 = 0.413, P = 0.003) and maximal (R 2 = 0.434, P = 0.002) respiration, and with decreased NLRP3 expression (R 2 = 0.330, P = 0.020). (Nicotinamide Riboside in Systolic Heart Failure; NCT03423342).
Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.
Emerging Role of Nicotinamide Riboside in Health and Diseases. [2022]Among all the NAD+ precursors, nicotinamide riboside (NR) has gained the most attention as a potent NAD+-enhancement agent. This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans. Boosting intracellular NAD+ concentrations using NR has been shown to provide protective effects against a broad spectrum of pathological conditions, such as neurodegenerative diseases, diabetes, and hearing loss. In this review, an integrated overview of NR research will be presented. The role NR plays in the NAD+ biosynthetic pathway will be introduced, followed by a discussion on the synthesis of NR using chemical and enzymatic approaches. NR's effects on regulating normal physiology and pathophysiology will also be presented, focusing on the studies published in the last five years.
A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. [2021]Label="OBJECTIVE">A decay in intracellular NAD+ levels is one of the hallmarks of physiological decline in normal tissue functions. Accordingly, dietary supplementation with NAD+ precursors can prevent, alleviate, or even reverse multiple metabolic complications and age-related disorders in diverse model organisms. Within the constellation of NAD+ precursors, nicotinamide riboside (NR) has gained attention due to its potent NAD+ biosynthetic effects in vivo while lacking adverse clinical effects. Nevertheless, NR is not stable in circulation, and its utilization is rate-limited by the expression of nicotinamide riboside kinases (NRKs). Therefore, there is a strong interest in identifying new effective NAD+ precursors that can overcome these limitations.