AgingNCT07144527
Nicotinamide Mononucleotide Supplementation for Exercise Tolerance Improvement in Healthy Older Adults
A study testing NMN and TMG (Euexia) and Nicotinamide Mononucleotide (NMN) in people with Aging and Frailty, run by Scott Silveira at 1 site in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled, two-arm crossover clinical trial evaluating the effects of nicotinamide mononucleotide (NMN) combined with trimethylglycine (TMG) supplementation, compared to NMN alone. Read more about this study
- Who is it for?
- Ages 60 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Frailty, Exercise Tolerance
- What is being tested?
- NMN and TMG (Euexia) and Nicotinamide Mononucleotide (NMN)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2026to 1 Jan 2027
- Phase
- Interventional
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 60 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults aged 60 to 80 years, of any sex
- Written clearance from primary care physician confirming medical fitness to participate in an exercise-based clinical study
- Normal or near-normal cardiovascular function to safely engage in moderate to vigorous exercise, demonstrated by either: stress echocardiogram or coronary CT angiogram within the past 12 months showing normal left ventricular function, no significant valvular heart disease, no ischemic changes, and no other clinically significant abnormalities, plus confirmation that no new cardiovascular symptoms (e.g., chest pain, dyspnea, syncope) or changes in health status have occurred since testing
- Montreal Cognitive Assessment (MoCA) score of 26 or higher
- Free from acute or uncontrolled chronic medical conditions that would pose a risk or interfere with study participation
- Physically capable of engaging in structured exercise involving moderate to vigorous intensity stationary cycling
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- Successful completion of a graded exercise test (e.g., stationary bike) without significant adverse events or contraindications
- Ability to attend at least four in-person laboratory visits in Beverly Hills, California
- Non-smoker for at least 12 months
- Able to provide informed consent and comply with study procedures
- Willing to refrain from initiating new exercise, dietary supplement, or medication regimens during the study
Who cannot join
- Severe cardiovascular disease (e.g., recent myocardial infarction <6 months, unstable angina, uncontrolled hypertension >160/100 mmHg)
- Severe respiratory conditions (e.g., advanced COPD or other conditions preventing exercise participation)
- Significant neurological impairments that hinder comprehension of instructions or participation in exercise
- Terminal illness or conditions limiting life expectancy or ability to complete the study
- Severe cognitive impairment preventing informed consent, protocol adherence, or comprehension of interventions
- Significant orthopedic limitations or injuries that prevent safe exercise participation
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- Use of NMN, NR, or other NAD+-altering supplements within the past 14 weeks
- Anticipated or current alcohol consumption >2 drinks per week, or unwillingness to abstain from alcohol during the study
- Current substance abuse affecting study participation or adherence
- Other acute or chronic health conditions judged by the investigators to pose risk or interfere with study objectives
- Non-compliance with study requirements, withdrawal of informed consent, or unforeseen circumstances compromising completion
- Any condition which, in the opinion of the investigator, would interfere with study participation or interpretation of results
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Medical Office of Dr. Robert Huizenga MD
Beverly Hills, California, 90210
Nancy Castellanos, BA, 310-666-6585, huizenganurse@robertsondx.com
Ashley Erazo, Medical Assistant, 310-657-9191, huizenganurse@robertsondx.com
About this study
This is a randomized, double-blind, placebo-controlled, two-arm crossover clinical trial evaluating the effects of nicotinamide mononucleotide (NMN) combined with trimethylglycine (TMG) supplementation, compared to NMN alone. The study will assess safety and efficacy in improving exercise tolerance and modulating biomarkers of aging in healthy older adults.
The primary outcome is cycle ergometry constant work rate (CWR) exercise tolerance, measured as time to fatigue. Secondary outcomes include changes in peak oxygen consumption (VO₂peak), critical power, anaerobic work capacity, lactate threshold, and NAD⁺ metabolite levels.
The supplements have been used in prior exploratory studies and real-world applications, which have helped inform the design of this current trial.
Read the detailed description
This randomized, double-blind, placebo-controlled, two-arm crossover trial will compare the effects of two NAD⁺-modulating interventions-nicotinamide mononucleotide (NMN) with trimethylglycine (TMG) and conventional NMN supplementation-on exercise tolerance and metabolic biomarkers in healthy older adults. The NMN and TMG arm will involve a twice-daily oral dose containing 1000 mg of NMN and 500 mg of TMG, while the comparison arm will involve twice-daily oral dose of 1000 mg of NMN per day. Doses will be self-administered each morning and evening with water.
The primary endpoint is time to fatigue during constant work rate cycle ergometry (CWR-Tlim), a validated surrogate for submaximal exercise tolerance. Secondary endpoints include peak oxygen uptake (VO₂peak), lactate threshold, anaerobic work capacity, and critical power, in addition to circulating NAD⁺ and its related metabolites.
The trial is designed to evaluate the short-term physiological effects and biological activity of NMN with TMG compared to NMN alone under tightly controlled exercise testing and training conditions. Data from this study will be used to inform the therapeutic potential of an over-the-counter product (Euexia®) in improving physical performance in healthy older adults (60-80 years). Future directions may include further clinical evaluation or regulatory submissions, depending on outcomes from this pilot investigation.
- Conditions
- Aging, Frailty, Exercise Tolerance, Healthy Male and Female Subjects
- Being tested
- NMN and TMG (Euexia), Nicotinamide Mononucleotide (NMN), Placebo
- Keywords
- Nicotinamide Mononucleotide, NAD+ Metabolism, Exercise Tolerance, Aging, Older Adults, Betaine, High Intensity Interval Training, VO2peak, Lactate Threshold, Critical Power, Anaerobic Work Capacity, Healthy Volunteers, Trimethylglycine
- Medical subject headings
- Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMN and TMG (Euexia)Dietary supplement
Formulation containing NMN and TMG.
Nicotinamide Mononucleotide (NMN)Dietary supplement
Conventional NMN supplement.
PlaceboDietary supplement
Organoleptically matched inert control.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - NMN with TMG -> Placebo | Experimental | Participants receive NMN with TMG during Period 1, followed by Placebo during Period 2 after a washout. Assigned Interventions: NMN with TMG; Placebo. Receives: Dietary Supplement: NMN and TMG (Euexia); Dietary Supplement: Placebo |
| Arm 2 - Placebo -> NMN with TMG | Experimental | Participants receive Placebo during Period 1, followed by NMN with TMG during Period 2 after a washout. Assigned Interventions: Placebo; NMN with TMG. Receives: Dietary Supplement: NMN and TMG (Euexia); Dietary Supplement: Placebo |
| Arm 3 - NMN -> Placebo | Experimental | Participants receive Nicotinamide Mononucleotide (NMN) during Period 1, followed by Placebo during Period 2 after a washout. Assigned Interventions: NMN; Placebo. Receives: Dietary Supplement: Nicotinamide Mononucleotide (NMN); Dietary Supplement: Placebo |
| Arm 4 - Placebo -> NMN | Experimental | Participants receive Placebo during Period 1, followed by NMN during Period 2 after a washout. Assigned Interventions: Placebo; NMN. Receives: Dietary Supplement: Nicotinamide Mononucleotide (NMN); Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Fatigue During Constant Work Rate Cycle Ergometry (tLIM).
Duration (in seconds) that participants can sustain a constant submaximal workload on a cycle ergometer until volitional fatigue. This is a validated surrogate for submaximal exercise tolerance.
Measured: Measured at the beginning and end of each 4-week intervention period.
Secondary outcomes (5)
Peak Oxygen Uptake (VO2max)
Maximum oxygen consumption (ml/kg/min) achieved during graded exercise testing.
Measured: Measured at the beginning and end of each 4-week intervention period.
Lactate Threshold
Workload or oxygen consumption corresponding to the point at which blood lactate concentration rises above baseline, assessed via graded exercise testing and gas exchange sampling.
Measured: Measured at the beginning and end of each 4-week intervention period.
Anaerobic Work Capacity
Cumulative work performed above the critical power, calculated from cycle ergometer testing.
Measured: Measured at the beginning and end of each 4-week intervention period.
Critical Power
The asymptote of the power-duration relationship. A work rate reflecting sustainable aerobic work capacity.
Measured: Measured at the beginning and end of each 4-week intervention period.
Circulating NAD+ and Related Metabolites
Plasma concentrations of NAD+, NMN, and related metabolites measured by targeted metabolomics.
Measured: Measured at the beginning and end of each 4-week intervention period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2025
- Study start21 Feb 2026
- Primary completion30 Dec 2026 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, double-blind trial with two parallel groups, each using a two-period crossover design. One group receives NMN with TMG and a placebo in a random sequence, and the other group receives NMN and a placebo in a random sequence.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Scott Silveira
- Sponsor type
- University, hospital or other
- Collaborators
- Concordia University Chicago
- Responsible party
- Sponsor-investigator, Scott Silveira, Concordia University Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07144527
- Sponsor's protocol ID
- 2305604-1
- Status last verified
- Feb 2026
- First submitted
- 19 Aug 2025
- Last updated
- 7 Oct 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 (IPD) underlying the primary and secondary outcome results reported in this study will be shared. This includes data related to exercise testing outcomes (tLIM, VO2max, lactate threshold, anaerobic work capacity, critical power) and metabolomics (circulating NAD+ and related metabolites). Demographic and baseline characteristics will also be included in de-identified form.