SarcopeniaNR-VETNCT04691986
Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans
A study testing Nicotinamide Riboside in people with Sarcopenia and Nicotinamide Adenine Dinucleotide Concentration, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Sarcopenia, Nicotinamide Adenine Dinucleotide Concentration, Muscle Quality and NAD+ Content
- What is being tested?
- Nicotinamide Riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2023to 30 Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 85 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Ages 65-85
- Male or female
- Any race
- Ability to use an exercise bike
- Medically cleared for muscle biopsy
Who cannot join
- Severe Co-morbidity
- examples include, but not limited to:
- congestive heart failure class equal to or above III
- chronic obstructive pulmonary disorder (COPD) gold stage IV
- chronic kidney disease equal to or above stage
- A VA-SLUMS cognitive screen score of less than or equal to 20
- Body mass index greater than or equal to 40
Trial locations and contacts
1 site in 1 country.
United States1 site
Kansas City VA Medical Center, Kansas City, MO
Kansas City, Missouri, 64128-2226
About this study
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.
Read the detailed description
Frailty is increasingly seen within the aging population and is driven largely by musculoskeletal declines. Nearly 9 million Veterans are now 65 years of age or older with impairments in functional capacity, reduction in quality of life, and an increase in the use of health care services and associated costs. An estimated 45-50% of those over the age of 85 are frail, which could represent well over 1 million Veterans. Aging, which significantly contributes to frailty, is highly correlated with reduced levels of nicotinamide adenine dinucleotide (NAD+), an essential mediator in mitochondrial function. Restoration of cellular NAD+ levels is gaining support as a therapeutic strategy to maintain and even enhance functional capacity during aging. Nicotinamide riboside (NR) - an NAD+ precursor - enhances physical activity and mitochondrial health in mice. Furthermore, NR was recently shown to be safe in human clinical trials for boosting NAD+, yet the benefits for human physical performance and muscle physiology are unknown. Therefore, the goal of this project is to establish a double-blind randomized control trial to assess the impacts of NR on functional capacity, muscle function and structure, and mRNA signaling in healthy older adults. Towards this goal, this study will investigate healthy older individuals between the ages of 65 and 85 who will receive NR or a placebo for a period of 3 months. Participants will be tested for frailty, gait speed, and muscle strength at each time point. Additionally, muscle biopsies and serum will be collected to assess changes in muscle fiber histology, mitochondrial biomass and activity, and mRNA profiles. This project will provide greater insight into NR supplementation as a therapeutic strategy to stave off frailty and maintain resilience during aging.
- Conditions
- Sarcopenia, Nicotinamide Adenine Dinucleotide Concentration, Muscle Quality and NAD+ Content
- Being tested
- Nicotinamide Riboside, Placebo
- Keywords
- muscle, strength, endurance, gait speed, grip strength, frailty, muscle fibers, mitochondria, inflammation, resilience, aging
- Medical subject headings
- Sarcopenia, Frailty, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide RibosideDietary supplement
Also called NR
Nicotinamide Riboside is a form of vitamin B3 and is naturally occurring in humans.
PlaceboOther
Placebo pills contain micro cellulose powder.
| Study group | Role | What they receive |
|---|---|---|
| NR Supplementation | Experimental | Participants in this group will receive NR supplementation at 1000 mg per day (given as 2x250mg capsules morning and 2x250mg at night). Receives: Dietary Supplement: Nicotinamide Riboside |
| Placebo supplementation | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sub-maximal oxygen uptake test (VO2max)
Participants are asked to exercise on an recumbent exercise bike as the resistance increases over time. During the exercise, participants are asked to breath through a mask that is connected to a oxygen and carbon dioxide measuring device. Participant will be asked to continue until they report exhaustion, reach 85% of heart rate maximum, or if there are medical concerns. The assessment last for approximately 15 minutes and provides data the pertain to an individuals lung capacity, breathing rate, and endurance.
Measured: Change from baseline to endpoint at 12 weeks
Muscle strength
Leg and arm strength will be measured using a small handheld dynamometer where the device is placed on the wrist or ankle as the participant is asked to extend or contract the limb with full force.
Measured: Change from baseline to endpoint at 12 weeks
Gait speed
Participants are asked to perform a timed walk of approximately 15 feet in length
Measured: Change from baseline to endpoint at 12 weeks
Secondary outcomes (9)
Frailty assessment
Frailty is a syndrome marked by greater susceptibility to adverse outcomes like falls and disability. Frailty diagnosis in this study is conducted as having 3 or more of the following risk factors - unexpected weight loss in a 1 year time frame, weak grip strength measured by a hand dynamometer device, slow gait speed in a 15 foot walk test, low activity levels assessed with a survey question, and poor endurance also assessed by a survey question.
Measured: Change from baseline to endpoint at 12 weeks
Short Physical Performance Battery
The Short physical performance battery (SPPB) is a battery of test often used in geriatric research to capture functional capacity in older adults. The test includes a balance and coordination assessment via asking participants to hold stances with different foot positions, a gait speed test of approximately 8 feet, and a chair rise timed test where a participant is asked to rise from a chair 5 times.
Measured: Change from baseline to endpoint at 12 weeks
Quality of life assessment
Quality of life assessment is performed using the Quality of life, enjoyment, and satisfaction questionnaire - short form (Q-LES-Q-SF) survey instrument. The survey instrument scores from 0 to 70 with a greater score representing better quality of life.
Measured: Change from baseline to endpoint at 12 weeks
Cognitive screen
Cognitive status will be assessed using the VA - St. Louis University Mental Survey (VA-SLUMS) involving memory tests, shape recognition, and story recall. The survey scores range from 0-30, with a higher score representing greater cognitive capability.
Measured: Change from baseline to endpoint at 12 weeks
Serum inflammatory biomarkers
Chronic inflammation may be indicative of distress and lead to chronic diseases. The study will examine changes in inflammatory markers, C-reactive protein, interleukin-6, and interleukin-10.
Measured: Change from baseline to endpoint at 12 weeks
Body Composition (Lean and fat mass)
Body composition will be measured using bioelectric impedance (BIA) - a technique where participants are asked to stand on the measurement device and hold on to two metal handles. A light - and non-detectable - current is then transmitted allowing for collection of body fat and lean mass in the subject. The assessment takes roughly 2-3 minutes.
Measured: Change from baseline to endpoint at 12 weeks
Blood occlusion resilience
The assessment is a measurement of the decline and restoration of blood oxygenation in the arm in response to the application of a blood pressure cuff to restrict blood flow. Blood oxygenation is measured by a technique called functional near infrared spectroscopy (fNIRS), that requires the placement of a small sensor on the lower forearm. The assessment takes roughly 6-7 minutes.
Measured: Change from baseline to endpoint at 12 weeks
6-minute walk and heart rate recovery
Participants will be asked to walk continuously at a brisk pace for 6 minutes as a measure of endurance. Additionally, they will be asked to wear a pulse-blood oxygenation monitor that will allow continuous measurement of heart rate. Following the assessment, the participant will be asked to be seated for 5 minutes to measure heart rate recovery. The assessment will take roughly 15 minutes.
Measured: Change from baseline to endpoint at 12 weeks
Balance resistance
Participants will be asked to stand on a BioSway device that measures sway speed (mm/s). They will be asked to hold balance for 45 seconds in four conditions, A) comfortable stance, B) comfortable stance with eyes closed, C) Narrow stance, and D) Narrow stance with eyes closed. The assessment will take roughly 5 minutes.
Measured: Change from baseline to endpoint at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2020
- Study start1 Sep 2023
- Primary completion31 Mar 2026
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcopeniaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study will be conducted as a double-blind randomized controlled trial. Participants will be randomly assorted to receive either the nicotinamide riboside supplementation or a placebo pill.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University at Buffalo
- Responsible party
- Sponsor
- Investigators
- Kenneth L Seldeen, PhD, Principal investigator, Kansas City VA Medical Center, Kansas City, MO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04691986
- Sponsor's protocol ID
- E3396-R
- Other IDs
- RX003396
- Acronym
- NR-VET
- Status last verified
- Jul 2026
- First submitted
- 10 Dec 2020
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data will be shared in publications and seminars culminating from this study. Additionally, de-identified raw data may be made accessible on a public database for research purposes. Individual participant data will be made available to the participant upon request, with the exception of treatment arm, which can be disclosed at the end of the study to protect blinding of investigators. Individual participant data may also be disclosed to current and future collaborators upon acceptance of a formal request.
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impacts of Nicotinamide Riboside on Functional Capacity and Muscle Physiology in Older Veterans
- ClinicalTrials.gov ID
- NCT04691986
- Acronym / sponsor ID
- NR-VET / E3396-R
- Conditions
- Sarcopenia, Nicotinamide Adenine Dinucleotide Concentration, Muscle Quality and NAD+ Content
- Keywords
- muscle, strength, endurance, gait speed, grip strength, frailty, muscle fibers, mitochondria
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 74 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University at Buffalo
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 31 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Frailty is increasingly seen within the aging population and is driven largely by musculoskeletal declines. Nearly 9 million Veterans are now 65 years of age or older with impairments in functional capacity, reduction in quality of life, and an increase in the use of health care services and associated costs. An estimated 45-50% of those over the age of 85 are frail, which could represent well over 1 million Veterans. Aging, which significantly contributes to frailty, is highly correlated with reduced levels of nicotinamide adenine dinucleotide (NAD+), an essential mediator in mitochondrial function. Restoration of cellular NAD+ levels is gaining support as a therapeutic strategy to maintain and even enhance functional capacity during aging. Nicotinamide riboside (NR) - an NAD+ precursor - enhances physical activity and mitochondrial health in mice. Furthermore, NR was recently shown to be safe in human clinical trials for boosting NAD+, yet the benefits for human physical performance and muscle physiology are unknown. Therefore, the goal of this project is to establish a double-blind randomized control trial to assess the impacts of NR on functional capacity, muscle function and structure, and mRNA signaling in healthy older adults. Towards this goal, this study will investigate healthy older individuals between the ages of 65 and 85 who will receive NR or a placebo for a period of 3 months. Participants will be tested for frailty, gait speed, and muscle strength at each time point. Additionally, muscle biopsies and serum will be collected to assess changes in muscle fiber histology, mitochondrial biomass and activity, and mRNA profiles. This project will provide greater insight into NR supplementation as a therapeutic strategy to stave off frailty and maintain resilience during aging.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- The study will be conducted as a double-blind randomized controlled trial. Participants will be randomly assorted to receive either the nicotinamide riboside supplementation or a placebo pill.
| Arm | Type | Receives |
|---|---|---|
| NR Supplementation | Experimental | Dietary Supplement: Nicotinamide RibosideParticipants in this group will receive NR supplementation at 1000 mg per day (given as 2x250mg capsules morning and 2x250mg at night). |
| Placebo supplementation | Placebo comparator | Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- Ages 65-85
- Male or female
- Any race
- Ability to use an exercise bike
- Medically cleared for muscle biopsy
Key exclusion criteria (7 listed)
- Severe Co-morbidity
- A VA-SLUMS cognitive screen score of less than or equal to 20
- Body mass index greater than or equal to 40
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide RibosideAlso: NRNicotinamide Riboside is a form of vitamin B3 and is naturally occurring in humans. | Dietary supplement | NR Supplementation |
| PlaceboPlacebo pills contain micro cellulose powder. | Other | Placebo supplementation |
Primary outcome
Sub-maximal oxygen uptake test (VO2max)
Time frame: Change from baseline to endpoint at 12 weeks
Participants are asked to exercise on an recumbent exercise bike as the resistance increases over time. During the exercise, participants are asked to breath through a mask that is connected to a oxygen and carbon dioxide measuring device. Participant will be asked to continue until they report exhaustion, reach 85% of heart rate maximum, or if there are medical concerns. The assessment last for approximately 15 minutes and provides data the pertain to an individuals lung capacity, breathing rate, and endurance.
Muscle strength
Time frame: Change from baseline to endpoint at 12 weeks
Leg and arm strength will be measured using a small handheld dynamometer where the device is placed on the wrist or ankle as the participant is asked to extend or contract the limb with full force.
Gait speed
Time frame: Change from baseline to endpoint at 12 weeks
Participants are asked to perform a timed walk of approximately 15 feet in length
9 secondary outcomes
Frailty assessment
Time frame: Change from baseline to endpoint at 12 weeks
Short Physical Performance Battery
Time frame: Change from baseline to endpoint at 12 weeks
Quality of life assessment
Time frame: Change from baseline to endpoint at 12 weeks
Cognitive screen
Time frame: Change from baseline to endpoint at 12 weeks
Serum inflammatory biomarkers
Time frame: Change from baseline to endpoint at 12 weeks
Body Composition (Lean and fat mass)
Time frame: Change from baseline to endpoint at 12 weeks
Blood occlusion resilience
Time frame: Change from baseline to endpoint at 12 weeks
6-minute walk and heart rate recovery
Time frame: Change from baseline to endpoint at 12 weeks
Balance resistance
Time frame: Change from baseline to endpoint at 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data will be shared in publications and seminars culminating from this study. Additionally, de-identified raw data may be made accessible on a public database for research purposes. Individual participant data will be made available to the participant upon request, with the exception of treatment arm, which can be disclosed at the end of the study to protect blinding of investigators. Individual participant data may also be disclosed to current and future collaborators upon acceptance of a formal request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth L Seldeen, PhD principal investigator
Kansas City VA Medical Center, Kansas City, MO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotinamide Riboside in people with Sarcopenia and Nicotinamide Adenine Dinucleotide Concentration, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sub-maximal oxygen uptake test (VO2max) (time frame: Change from baseline to endpoint at 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.