Nicotinamide Riboside for Heart Failure

(NRII Trial)

Overseen By Shannon L Yedinak

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Washington

Disqualifiers: Cirrhosis, Severe renal disease, Untreated thyroid, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a supplement called nicotinamide riboside (NR) can improve heart function in individuals with severe heart failure. Researchers aim to determine if NR can increase key molecules in cells that may enhance heart health and reduce inflammation. Participants will receive either NR or a placebo to compare effects. Ideal candidates include those with end-stage heart failure who are scheduled to receive a device that assists the heart in pumping blood. As an Early Phase 1 trial, this research seeks to understand how NR works in people, providing participants the opportunity to be among the first to receive this treatment.

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.

Is there any evidence suggesting that nicotinamide riboside is likely to be safe for humans?

Research has shown that nicotinamide riboside (NR) is safe for humans. One study found that taking 2 grams of NR daily for 12 weeks was safe and well-tolerated by participants. The study also noted an increase in NAD+ levels in their blood, indicating the treatment's effectiveness. No major safety issues were reported.

Although this trial is still in its early stages, current evidence suggests that NR is generally safe for short-term use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Nicotinamide Riboside is unique because it targets heart failure by boosting levels of NAD+, a molecule involved in energy production and cellular repair. Unlike conventional treatments like ACE inhibitors or beta-blockers that primarily manage symptoms and reduce strain on the heart, Nicotinamide Riboside aims to enhance the heart's energy metabolism directly. Researchers are excited about this approach because it could potentially rejuvenate heart cells, offering a new way to improve heart function at a cellular level.

What evidence suggests that nicotinamide riboside might be an effective treatment for heart failure?

Research shows that nicotinamide riboside (NR), which participants in this trial may receive, can increase NAD+ levels in the blood. NAD+ plays a crucial role in energy production and cell repair. Studies have found that NR can help restore NAD+ levels in people with heart failure. Early findings suggest that increasing NAD+ can improve heart function by supporting the mitochondria, the cell's energy centers. In animal studies, NR enhanced heart function. Although data on humans remains limited, these early results are promising for treating heart failure. ^{4 5 6 7 8}

Who Is on the Research Team?

Kevin D O'Brien, MD

Principal Investigator

University of Washington

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside

Trial Overview The 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.

How Is the Trial Designed?

Group I: Nicotinamide riboside Experimental Treatment 1 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: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a trial involving 30 patients with heart failure, the NAD+ precursor nicotinamide riboside (NR) was found to be safe and well tolerated, significantly increasing NAD+ levels in the blood.

The increase in NAD+ levels correlated with improved cellular respiration and reduced expression of the inflammatory marker NLRP3, suggesting that NR may help improve mitochondrial function in heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. Wang, DD., Airhart, SE., Zhou, B., et al.[2023]

Nicotinamide riboside (NR) supplementation significantly restored NAD+ levels in mice after a myocardial infarction (MI), improving survival rates from 61% to 92% over a 7-day treatment period.

NR also enhanced mitochondrial function and reduced inflammation in the heart, suggesting it may have cardioprotective effects that could be beneficial for managing MI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction. Tannous, C., Ghali, R., Karoui, A., et al.[2023]

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[2021]

Nicotinamide riboside (NR) is a safe and effective NAD+ precursor that is orally bioavailable in humans, showing promise in enhancing NAD+ levels.

Research indicates that boosting NAD+ with NR may protect against various health issues, including neurodegenerative diseases, diabetes, and hearing loss, highlighting its potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Role of Nicotinamide Riboside in Health and Diseases. Sharma, C., Donu, D., Cen, Y.[2022]

Nicotinamide riboside hydride (NRH) is identified as a more effective and faster precursor for NAD+ synthesis compared to nicotinamide riboside (NR), utilizing a unique NRK1-independent pathway for NAD+ production.

NRH is orally bioavailable in mice and has shown potential in preventing acute kidney injury caused by cisplatin, suggesting its therapeutic promise in enhancing NAD+ levels and addressing metabolic complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A reduced form of nicotinamide riboside defines a new path for NAD+ biosynthesis and acts as an orally bioavailable NAD+ precursor. Giroud-Gerbetant, J., Joffraud, M., Giner, MP., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9831861/

Safety and Tolerability of Nicotinamide Riboside in Heart ... In in this study, NR at 2 g/d over 12 weeks was safe, well tolerated, and significantly increased whole blood NAD+ levels in ambulatory stage C ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352172/

Nicotinamide Riboside—The Current State of Research and ... Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03423342

Nicotinamide Riboside in Systolic Heart Failure The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.032626

Raising NAD in Heart Failure | Circulation In this issue of Circulation, Diguet et al report exciting data suggesting that supplementation with a NAD+ precursor, nicotinamide riboside (NR) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452302X24000391

The Efficacy of Risk Factor Modification Compared to ... Findings show significant NAD+ and nicotinamide phosphoribosyltransferase depletion in human diastolic HF myocardium, but NR successfully restored NAD+ levels.

6. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038603

Nicotinamide Riboside: A Promising Treatment for Type 1 ... Our findings indicate that NR could potentially be a promising therapy for acute kidney injury following an early stage of MI.

7. jacc.org jacc.org/doi/10.1016/j.jacbts.2022.06.012

Safety and Tolerability of Nicotinamide Riboside in Heart ... In in this study, NR at 2 g/d over 12 weeks was safe, well tolerated, and significantly increased whole blood NAD+ levels in ambulatory stage C ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36644285/

Safety and Tolerability of Nicotinamide Riboside in Heart ... Raising NAD+ levels with the NAD+ precursor, nicotinamide riboside (NR), may represent a novel HF treatment.