Nicotinamide Riboside for Sarcopenia

(NR-VET Trial)

Recruiting at 1 trial location

Overseen By Ayesha Rahman, MS

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Congestive heart failure, COPD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

144 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug Nicotinamide Riboside unique in treating sarcopenia?

Nicotinamide Riboside (NR) is unique because it is a precursor to NAD+ (a vital molecule for energy production in cells) and has shown potential in improving muscle health by increasing NAD+ levels, which may help counteract muscle loss associated with sarcopenia. Unlike other treatments, NR is a form of vitamin B3 and is generally recognized as safe for use in foods and supplements, offering a novel approach to managing age-related muscle decline. ^{1 2 3 4 5}

What is the purpose of this trial?

Frailty is an age-associated clinical condition of poor physiological reserve that increases risks for falls, hospitalization and mortality. Nicotinamide adenine dinucleotide (NAD) is a critical co-factor needed for many cellular processes. The natural levels of NAD decline aging and this has been linked to physical performance decline in animals. Human trials have demonstrated that nicotinamide riboside (NR), a form of vitamin B3, is safe and effectively increases NAD+ levels. In animal studies, NR improves treadmill performance and muscle quality. Here the investigators propose a double-blind randomized control trial to assess the benefits of NR supplementation on human muscle function and physiology. The investigators anticipate the research findings will support the use of this nutritional supplement to improve the health of Veterans during aging.

Research Team

Kenneth L Seldeen, PhD

Principal Investigator

Kansas City VA Medical Center, Kansas City, MO

Eligibility Criteria

This trial is for older veterans aged 65-85 who can use an exercise bike and are medically cleared for a muscle biopsy. It's not suitable for individuals with severe illnesses, advanced heart failure or COPD, serious kidney disease, significant cognitive impairment, or those extremely overweight.

Inclusion Criteria

I am either male or female.

I am between 65 and 85 years old.

Any race

Exclusion Criteria

Your VA-SLUMS cognitive screen score is 20 or lower.

I have chronic kidney disease stage 3 or higher.

I have severe COPD.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive NR or placebo supplementation for 3 months, with assessments of frailty, gait speed, and muscle strength at each time point

12 weeks

Regular visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Nicotinamide Riboside

Trial Overview The study tests if Nicotinamide Riboside (a vitamin B3 form) can improve muscle function and increase NAD+ levels in the body compared to a placebo. Participants will be randomly assigned to either the supplement group or placebo group without knowing which one they're receiving.

Participant Groups

Group I: NR Supplementation Experimental Treatment 1 Intervention

Participants in this group will receive NR supplementation at 1000 mg per day (given as 2x250mg capsules morning and 2x250mg at night).

Group II: Placebo supplementation Placebo Group 1 Intervention

Participants in this group will receive placebo given as 2 pills in the morning and 2 pills at night. Placebo pills contain micro cellulose which is likewise found in NR containing capsules.

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?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

University at Buffalo

Collaborator

Trials

139

Recruited

105,000+

Findings from Research

In a 12-week randomized, placebo-controlled trial with 40 middle-aged, obese, insulin-resistant men, nicotinamide riboside (NR) supplementation did not significantly affect mitochondrial function, content, or morphology in skeletal muscle.

Despite a 14% decrease in the protein abundance of NAMPT, an enzyme involved in NAD+ biosynthesis, NR supplementation did not change NAD+ levels or the respiratory capacity of muscle mitochondria, suggesting limited efficacy in improving mitochondrial health in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. Dollerup, OL., Chubanava, S., Agerholm, M., et al.[2021]

Skeletal muscle cells primarily use the enzymes NAMPT, NRK1, and NRK2 to synthesize NAD+ from dietary supplements like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), which are crucial for maintaining muscle health as we age.

Inhibition of NAMPT reduces NAD+ levels in muscle, but this can be restored by NMN and NR, indicating that both supplements are effective in enhancing NAD+ availability through pathways that depend on NRK1 and NRK2.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. Fletcher, RS., Ratajczak, J., Doig, CL., et al.[2022]

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze, D., Brenner, C., Kruger, CL.[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]

In a mouse model of cancer cachexia, preemptive administration of nicotinamide riboside (NR) significantly reduced weight loss and muscle atrophy by inhibiting key inflammatory factors and muscle-specific proteins associated with muscle degradation.

NR intake also enhanced the production of NAD+ biosynthesis enzymes and inhibited the activity of sirtuin 1, suggesting that NR could be a promising intervention to prevent cachexia in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia. Park, JM., Han, YM., Lee, HJ., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. [2023]

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

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia. [2021]