Nicotinamide Mononucleotide Supplementation for Exercise Tolerance Improvement in Healthy Older Adults

NCT07144527 | Recruiting DMC

• 1 other identifier: 2305604-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, two-arm crossover clinical trial evaluating the effects of a patented age-reversal therapy, EGA®, compared to conventional nicotinamide mononucleotide (NMN) supplementation. 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. EGA® is composed of three metabolomic compounds that are endogenous to humans. The formulation has been used in prior exploratory studies and real-world applications, which have helped inform the design of this current trial.

Conditions

Aging; Frailty; Exercise Tolerance; Healthy Male and Female Subjects

Keywords

Nicotinamide Mononucleotide; NAD+ Metabolism; Exercise Tolerance; Aging; Older Adults; Betaine; Hydrogen Peroxide (low-dose, dietary); High Intensity Interval Training; VO2peak; Lactate Threshold; Critical Power; Anaerobic Work Capacity; Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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 at the beginning and end of each 4-week intervention period.

Secondary Outcomes (5)

• Peak Oxygen Uptake (VO2max)

  Measured at the beginning and end of each 4-week intervention period.

• Lactate Threshold

  Measured at the beginning and end of each 4-week intervention period.

• Anaerobic Work Capacity

  Measured at the beginning and end of each 4-week intervention period.

• Critical Power

  Measured at the beginning and end of each 4-week intervention period.

• Circulating NAD+ and Related Metabolites

  Measured at the beginning and end of each 4-week intervention period.

Other Outcomes (4)

• Adverse Events

  From first dose through final study visit (up to 12 weeks per participant, including two 4-week intervention periods and a 4-week washout).

• Adherence to Supplementation

  Assessed weekly during each 4-week intervention period and at the end of each intervention period (Weeks 4 and 12), for a total study duration of up to 12 weeks per participant.

• Exercise Session Adherence

  Assessed weekly during each 4-week intervention period and summarized at the end of each period (Weeks 4 and 12); total study duration up to 12 weeks per participant.

Study Arms (4)

Arm 1 - EGA -> Placebo

EXPERIMENTAL

Participants receive EGA during Period 1, followed by Placebo during Period 2 after a washout. Assigned Interventions: EGA; Placebo.

Dietary Supplement: NMN, betaine, low-dose hydrogen peroxide (EGA); Dietary Supplement: Placebo

Arm 2 - Placebo -> EGA

EXPERIMENTAL

Participants receive Placebo during Period 1, followed by EGA during Period 2 after a washout. Assigned Interventions: Placebo; EGA.

Dietary Supplement: NMN, betaine, low-dose hydrogen peroxide (EGA); 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.

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.

Dietary Supplement: Nicotinamide Mononucleotide (NMN); Dietary Supplement: Placebo

Interventions

Nicotinamide Mononucleotide (NMN) DIETARY_SUPPLEMENT

Conventional NMN supplement.

Arm 3 - NMN -> Placebo; Arm 4 - Placebo -> NMN

Placebo DIETARY_SUPPLEMENT

Organoleptically matched inert control.

Arm 1 - EGA -> Placebo; Arm 2 - Placebo -> EGA; Arm 3 - NMN -> Placebo; Arm 4 - Placebo -> NMN

NMN, betaine, low-dose hydrogen peroxide (EGA) DIETARY_SUPPLEMENT

Proprietary formulation containing NMN, betaine, and low-dose hydrogen peroxide.

Arm 1 - EGA -> Placebo; Arm 2 - Placebo -> EGA

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Scott Silveira: lead
• Concordia University Chicago: collaborator

Study Sites (1)

Medical Office of Dr. Robert Huizenga MD

Beverly Hills, California, 90210, United States

RECRUITING

MeSH Terms

Conditions

Frailty

Interventions

Betaine; Hydrogen Peroxide; Nicotinamide Mononucleotide

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Peroxides; Oxides; Anions; Ions; Electrolytes; Inorganic Chemicals; Reactive Oxygen Species; Free Radicals; Oxygen Compounds; Ribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Randomized, double-blind trial with two parallel groups, each using a two-period crossover design. One group receives EGA and a placebo in a random sequence, and the other group receives NMN and a placebo in a random sequence.

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: August 27, 2025
• Study Start: February 21, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD and supporting information will be available within 12 months of publication of the primary results and will remain available for 5 years thereafter.
• Access Criteria: Data will be made available to qualified researchers upon submission of a methodologically sound research proposal. Requests should be directed to the Principal Investigator, and access will be granted after review and approval by the study steering committee. Data will be shared under a data use agreement to ensure participant confidentiality.

Locations

US (1)