Nicotinamide Riboside for Sarcopenia

(NR-VET Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Kenneth L Seldeen, PhD

Age: 65+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

Disqualifiers: Congestive heart failure, COPD, others

Approved in 2 Jurisdictions

Trial Summary

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.

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.

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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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

VA Western New York Healthcare System, Buffalo, NY Buffalo, NY

Kansas City VA Medical Center, Kansas City, MO Kansas City, MO

Who Is Running the Clinical Trial?

VA Office of Research and Development Lead Sponsor

University at Buffalo Collaborator

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] This is the first long-term human clinical trial to report on effects of nicotinamide riboside (NR) on skeletal muscle mitochondrial function, content and morphology. NR supplementation decreases nicotinamide phosphoribosyltransferase (NAMPT) protein abundance in skeletal muscle. NR supplementation does not affect NAD metabolite concentrations in skeletal muscle. Respiration, distribution and quantity of muscle mitochondria are unaffected by NR. NAMPT in skeletal muscle correlates positively with oxidative phosphorylation Complex I, sirtuin 3 and succinate dehydrogenase.

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] Label="OBJECTIVE">Augmenting nicotinamide adenine dinucleotide (NAD+) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD+. Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD+ from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis.

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] Nicotinamide riboside (NR) is a newly discovered nicotinamide adenine dinucleotide (NAD+) precursor vitamin. A crystal form of NR chloride termed NIAGEN is generally recognized as safe (GRAS) for use in foods and the subject of two New Dietary Ingredient Notifications for use in dietary supplements. To evaluate the kinetics and dose-dependency of NR oral availability and safety in overweight, but otherwise healthy men and women, an 8-week randomized, double-blind, placebo-controlled clinical trial was conducted. Consumption of 100, 300 and 1000 mg NR dose-dependently and significantly increased whole blood NAD+ (i.e., 22%, 51% and 142%) and other NAD+ metabolites within 2 weeks. The increases were maintained throughout the remainder of the study. There were no reports of flushing and no significant differences in adverse events between the NR and placebo-treated groups or between groups at different NR doses. NR also did not elevate low density lipoprotein cholesterol or dysregulate 1-carbon metabolism. Together these data support the development of a tolerable upper intake limit for NR based on human data.

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

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.

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

Nicotinamide Riboside Vitamin B3 Mitigated C26 Adenocarcinoma-Induced Cancer Cachexia. [2021] Nicotinamide riboside (NR), vitamin B3, is a substrate for nicotinamide adenine dinucleotide (NAD+)-consuming enzymes and is a coenzyme for hydride-transfer enzymes, including adenosine diphosphate (ADP)-ribose transferases, poly (ADP-ribose) polymerases, cADP-ribose synthases, and sirtuins, which play a central role in the aging process, neurodegenerative processes, and myopathy. Since cancer cachexia is a disease condition presenting with weight loss, skeletal muscle atrophy, and loss of adipose tissue in patients with advanced cancer, we hypothesized that NR intake could ameliorate sarcopenia. In this study, we investigated whether preemptive administration of NR ameliorated C26 adenocarcinoma-induced cancer cachexia and explored anti-cachexic mechanisms focused on the changes in muscle atrophy, cachexic inflammation, and catabolic catastrophe. Dietary intake of the NR-containing pellet diet significantly attenuated cancer cachexia in a mouse model. Starting with significant inhibition of cachexic factors, tumor necrosis factor alpha, and interleukin-6, NR significantly inhibited muscle-specific ubiquitin-proteasome ligases, such as atrogin-1, muscle RING-finger protein-1 (MuRF-1), mitofusin-2, and peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PCG-1α). Significant inhibition of epididymal fat lipolysis was noted with significant inhibition of adipose triglyceride lipase (ATGL) gene. Furthermore, NR administration significantly increased the levels of crucial enzymes involved in the biosynthesis of NAD+ and nicotinamide phosphoribosyl transferase and significantly inhibited the NAD+-sensitive deacetylase sirtuin 1 (SIRT1). Preemptive intake of NR in patients vulnerable to cachexia can be a preemptive option to ameliorate cancer cachexia.