Combination Gerotherapeutic Interventions for Healthspan Improvement

NCT07475546 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: ALRx011
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a 90-day interventional, randomized, controlled pilot trial exploring multi-modal gerotherapies and their impact on longevity-related outcomes. In this proof-of-concept phase, a small sample size of up to 30 subjects (10 subjects in each arm) will be randomized into one of the three arms: 1) Control, 2) Multi-therapy (B12, Naltrexone, Metformin, and NAD+), or 4) Comprehensive Therapy (Rapamycin, Naltrexone, Metformin, B12, NAD+, GSH, and Infinite Supplement).

Conditions

Healthspan Improvement; Aging; Longevity

Keywords

Gerotherapeutics; Rapamycin; Naltrexone; Metformin; NAD+; GSH; B12

Outcome Measures

Primary Outcomes (4)

• Change in cardiorespiratory fitness measured by maximal oxygen uptake (VO₂ max)

  Maximal oxygen uptake (VO₂ max) will be assessed using standardized cardiopulmonary exercise testing. This assessment will be conducted once at baseline and once at the 3-month follow-up. The outcome will be the change in VO₂ max from baseline to 3 months.

  3 months

• Change in cognitive performance measured by Creyos Cognitive Test composite score

  Cognitive performance will be assessed using the Creyos online cognitive assessment platform. Assessments will be conducted twice at baseline and twice during the final study period, with measurements occurring at least 7 days apart. Scores from the two assessments at each timepoint will be averaged to determine the baseline and endpoint values. The outcome will be the change in the overall composite cognitive performance score from baseline to 3 months.

  3 months

• Change in systemic chronic inflammation measured by iAge index score

  Immune function will be assessed via systemic chronic inflammation using the iAge Index Score derived from blood biomarkers. This assessment will be conducted once at baseline and once at the 3-month follow-up. The outcome will be the change in iAge index score from baseline to 3 months.

  3 months

• Change in lean body mass measured by dual-energy X-ray absorptiometry (DEXA)

  Lean body mass will be assessed using dual-energy X-ray absorptiometry (DEXA). This assessment will be conducted once at baseline and once at the 3-month follow-up. The outcome will be the change in total lean body mass from baseline to 3 months.

  3 months

Secondary Outcomes (15)

• Change in total sleep time measured using Oura wearable device

  3 months

• Change in health-related quality of life measured by the Short Form Health Survey (SF-36)

  3 months

• Change in biological age estimated from blood-based biomarker panels

  3 months

• Change in sleep quality measured by the Sleep Quality Scale (SQS)

  3 months

• Change in physical activity measured by the Rapid Assessment of Physical Activity (RAPA) questionnaire

  3 months

Other Outcomes (4)

• Change in resting heart rate measured using wearable device data

  3 months

• Change in physical activity measured by metabolic equivalent of task (MET) minutes using Oura wearable device data

  3 months

• Change in physiological stress score measured using Oura wearable device metric

  3 months

Study Arms (3)

Multi-Therapy: NAD+, LDN, B12, and metformin

EXPERIMENTAL

In intervention month one, participants naive to all medications will be titrated on to low maintenance doses of each. NAD+ will be taken as a nasal spray of 30mg/day; LDN, will start at 1.5mg once daily and titrate up each week to 4.5mg daily; B12, take 1 cap per day (100mcg); Metformin will be taken 500mg daily. They will then remain on the maintenance doses of the combination therapy for the next 60 days.

Drug: Naltrexone; Drug: Metformin; Drug: NAD+; Dietary Supplement: B12; Behavioral: Intervention: Guided Meditation Program; Behavioral: Intervention: Structured Exercise Program

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite

EXPERIMENTAL

In intervention month one, participants naive to all medications will be titrated on to low maintenance doses of each. LDR will start at 2mg once per week and titrate up weekly to 6mg once per week; LDN, will start at 1.5mg once daily and titrate up each week to 4.5mg daily; B12, take 1 cap per day (100mcg); Metformin will be taken 500mg daily; NAD+ will be taken as a nasal spray of 30mg/day; GSH will be taken as a topical patch for 4 hrs, once per week; Infinite supplement will be taken once daily. They will then remain on the maintenance doses of the combination therapy for the next 60 days.

Drug: Rapamycin; Drug: Naltrexone; Drug: Metformin; Drug: NAD+; Drug: GSH; Dietary Supplement: Infinite Supplement; Dietary Supplement: B12; Behavioral: Intervention: Guided Meditation Program; Behavioral: Intervention: Structured Exercise Program

Placebo

PLACEBO COMPARATOR

In the control cohort, participants will take Vitamin C (1x/day) and Vitamin E (1x/week) as placebo agents.

Drug: Placebo/control; Behavioral: Control: Podcast Listening Activity; Behavioral: Control: Standard Exercise Regimen

Interventions

Rapamycin DRUG

In the comprehensive therapy group, participants will start LDR at 2mg once per week and titrate up weekly to 6mg once per week.

Also known as: sirolimus, low-dose rapamycin (LDR)

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite

Naltrexone DRUG

In both intervention groups, participants will start LDN at 1.5mg once daily and titrate up each week to 4.5mg daily.

Also known as: low-dose naltrexone (LDN)

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

Metformin DRUG

In both intervention groups, participants will take Metformin at 500mg daily.

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

NAD+ DRUG

In both intervention groups, NAD+ will be taken as a nasal spray of 30mg/day.

Also known as: nicotinamide adenine dinucleotide (NAD+)

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

GSH DRUG

In the comprehensive therapy group, GSH will be taken as a topical patch for 4 hrs, once per week.

Also known as: Glutathione

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite

Infinite Supplement DIETARY_SUPPLEMENT

Participants in the comprehensive therapy group will take the Infinite supplement once daily. The Infinite supplement is a proprietary blend of seven putative geroprotective compounds implicated in enhancing cellular function critical for managing cellular damage accumulation prevention of age-related decline (including Alpha ketoglutarate, Quercetin, Glucosamine, Carnosine, Pterostilbene, Astaxanthin, and Curcumin)

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite

Placebo/control DRUG

In the control cohort, participants will take Vitamin C (1x/day) and Vitamin E (1x/week) as placebo agents.

Placebo

B12 DIETARY_SUPPLEMENT

In both intervention groups, participants will take vitamin B12 once daily.

Also known as: Methylcobalamin

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

Intervention: Guided Meditation Program BEHAVIORAL

Intervention group participants will follow a daily, app-based meditation program for 20 minutes a day.

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

Control: Podcast Listening Activity BEHAVIORAL

Control participants will listen to a neutral podcast for 20 minutes a day designed to control for time and attention.

Placebo

Control: Standard Exercise Regimen BEHAVIORAL

Control group participants will engage in a standard exercise regimen (150 minutes of aerobic activity such as walking per week).

Placebo

Intervention: Structured Exercise Program BEHAVIORAL

Intervention group participants will follow a structured daily exercise program including resistance training and a recommendation for 150 minutes of aerobic activity (e.g., walking) per week.

Comprehensive Therapy: LDR, LDN, B12, metformin, NAD+, GSH, and Infinite; Multi-Therapy: NAD+, LDN, B12, and metformin

Eligibility Criteria

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

You may qualify if:

• New, existing, or prospective AgelessRx patient
• Adults (60-80 years of age)
• Any sex
• Any ethnicity
• Willingness to provide informed consent and complete study assessments/procedures
• Willingness to attend virtual meeting check-ins/follow-ups
• Willingness and eligibility to take all medications used in this study
• Has at-risk indicators for decline on measures of cognitive, immune, and muscle function, as indicated by a combination of BMI of 26-30; SF36 score below the validated central tendency for 2 of: physical function, physical role limitations, energy, pain; final ISQ scores of \<6; individuals that report brain fog or difficulty with mental clarity; pre-diabetic, or other comorbidities that result in reduced overall health functioning as determined by a physician

You may not qualify if:

• Pregnant or breastfeeding individuals
• History of severe adverse reactions to study medications
• Significant psychiatric illness that may affect participation
• Determination of ineligibility for a study medication by AgelessRx medical team
• Concurrent participation in other conflicting clinical trials

Sponsors & Collaborators

• AgelessRx: lead

Study Sites (1)

AgelessRx

Ann Arbor, Michigan, 48104, United States

Location

MeSH Terms

Interventions

Sirolimus; Naltrexone; Metformin; NAD; Glutathione; Vitamin B 12; mecobalamin

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biguanides; Guanidines; Amidines; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Coenzymes; Enzymes and Coenzymes; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Macrocyclic Compounds

Study Officials

• Jenell Decker, MD

  AgelessRx

  PRINCIPAL INVESTIGATOR

• Stefanie Morgan, PhD

  AgelessRx

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: March 16, 2026
• Study Start: July 23, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)