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

Treatment Length: 14 days

32 Participants Needed

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?

Nicotinamide Riboside is unique because it boosts NAD+ levels in the body, which is important for energy production and cellular health, potentially offering a novel approach to treating heart failure by improving mitochondrial function and reducing inflammation. ^{1 2 3 4 5}

Research Team

Kevin D O'Brien, MD

Principal Investigator

University of Washington

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.

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 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.

Participant Groups

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+

Findings from Research

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]

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) 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Nicotinamide Riboside in Heart Failure With Reduced Ejection Fraction. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Emerging Role of Nicotinamide Riboside in Health and Diseases. [2022]

5. Germany 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. [2021]