A Pilot Study on Reverse Aging (The REVERSE Study)

Aging can be defined as a time-dependent functional decline in physiological function, which may increase the vulnerability to diseases and eventually death. The question is whether aging is a normal process, or exists as an "uber-illness?" Work done by Dr Sinclair at Harvard suggests the latter. Dr. Sinclair feels people should be able to age-in-place, or even reverse age. Aging is arguably the single biggest risk factor for all acquired and chronic diseases. Delaying the aging rate by 7 years would cut the incidence of chronic disease in half! Up until know the effects of anti-aging would need longitudinal studies until death.

Now, with the advent of a 3rd generation OMIC Age clock, there is a way to assess if an intervention is changing the rate of aging and other methylation patterns associated with aging.

Study Overview

• Status: Active, not recruiting
• Conditions: Aging
• Intervention / Treatment: Drug: Rapamycin (Tablets); Dietary supplement: Prolon diet

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • AIM for Wellbeing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects will be healthy and of any sex, any ethnicity, and any age from 50 to 80
• "Healthy" subjects will be defined as a real-world cohort of individuals likely to utilize such an intervention
• May be on other medications if they do not conflict with rapamycin.
• All medical conditions need to be stable and well controlled.
• Willing and able to provide informed consent

Exclusion Criteria:

• Severe illnesses, for which rapamycin may cause harm. This would not be limited to but include active neoplastic or auto-immune disease. If patients have a previous history of cancer or auto-immune disease, the risks and benefits and possible adverse reactions will be discussed at time of consent
• History of organ transplant
• Any unstable medical condition that would interfere with the study
• Hepatic impairment. Note: Patients with elevated liver enzymes and low albumin, will be further screened for hepatic impairment. Elevated liver enzymes < 2x upper limit of normal will not be considered hepatic impairment.
• Renal impairment, indicated by a serum creatinine > 1.4 mg/dL
• Anemia indicated by a hemoglobin < 12 g/dL
• Platelets < 80,000/cumm,
• ANC < 1,000 / cumm
• Total WBC < 3,000/cumm
• Pregnancy or breastfeeding or woman of childbearing potential with inadequate contraception
• Unstable mental illness
• A condition where rapamycin may interfere deleteriously with a medication that is taken by a potential subject
• Currently prescribed with high dose CYP3A4 pathway medications such as verapamil > 240 mg; simvastatin >40 mg, lovastatin > 40 mg or atorvastatin > 40 mg daily. Poor GI motility as demonstrated by delayed gastric emptying on a radionucleotide isotope scan.
• Intercurrent severe infection at initiation of study drug
• Any and all other reasons that the investigator may determine that the participant is not suitable for study enrollment.
• History of or active eating disorders as deemed by PI.
• BMI lower than 18.5
• Any medication that may dangerously lower glucose while on the FMD. This will include insulin, sulfonylureas (glyburide; glipizide); Thiazolidenediones ( eg piogltazone; rosiglitazone); GLP1 drugs (semaglutide; tirzepatide);; DPP-4 inhibitors (eg sitagliptin; saxagliptin); Alpha -glucosidase inhibitors (acarbose; miglitol). Patients on SGLT2 inhibitors (empagliflozin; canagliflozin) and Metformin (glucophage) may be included in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapamycin Only; 12 participants: 10 mg initial bolus dose of rapamycin followed by a weekly 6 mg rapamycin, enrolling 6 men, 6 women, with 6 ( 3 M, 3 F) who are 50-65 years; 6 ( 3 M, 3 F) who are >65 years	Drug: Rapamycin (Tablets); 10 mg initial bolus dose of rapamycin followed by a weekly 6 mg rapamycin
Active Comparator: Prolon Diet Only; 12 participants: 6 men, 6 women, with 6 (3 M, 3 F) who are 50-65 years; 6 who are >65 years Prolon® 5-day diet at 0, 1, 2, 3, 4 and 5 months;	Dietary supplement: Prolon diet; Prolon 5-day diet at 0, 1, 2, 3, 4,and 5 months
Experimental: Rapamycin and Prolon Diet; 24 participants: 10 mg initial bolus dose of rapamycin followed by a weekly 6 mg rapamycin along with Prolon 5-day diet at 0, 1, 2, 3, 4,and 5 months. : 12 men, 12 women, 12 ( 6 M, 6 F) who are 50-65 years; 12 ( 6 M, 6 F) who are >65 years.	Drug: Rapamycin (Tablets); 10 mg initial bolus dose of rapamycin followed by a weekly 6 mg rapamycin; Dietary supplement: Prolon diet; Prolon 5-day diet at 0, 1, 2, 3, 4,and 5 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Biological Age from Baseline to End of Study based on Tru Diagnostic Tru Age OMICm Age test results.	To evaluate the gradated effects of mTOR inhibition on a new OMIC methylation test that evaluates biological (vs chronological) age over a six-month period.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effects of AMPK (AMP Kinase inhibition) on aging. Change in OMICm methylation from baseline to Week 24 based on Tru Diagnostic Tru Age OMICm Age test results.	. This will duplicate studies already done utilizing a 5 day Fasting Mimicking Diet (FMD) (Prolon) on aging. The FMD diet will be administered 6 times - at monthly intervals. Change in OMICm methylation from baseline to Week 24	24 weeks
Effect of weekly low-dose rapamycin on aging based on Tru Diagnostic Tru Age OMICm Age test results.	Change in OMICm methylation from baseline to Week 24	24 weeks
Lowering of insulin resistance based on Tru Diagnostic Tru Age OMICm Age test results.	To evaluate the combined effects of AMPK and low-dose weekly rapamycin, at lowering insulin resistance, and thereby PI3K (PI3 kinase).	24 weeks
Effects on insulin resistance	To stratify outcomes of the prior three outcomes based on insulin resistance. This will be monitored using a Quest Lab Insulin Resistance panel to determine if insulin resistance is a confounding variable from any of the above. Variability of results in a, b, or c based on high, low or moderate insulin resistance.	24 weeks
Does reversal of age improve cognition based on the Cognitive Flexibility Inventory.	Changes in the Cognitive Flexibility Inventory from baseline to week 24. Scores range from 20-140, with a higher score representing a better outcome.	24 weeks
Patterns based on Age based on Tru Diagnostic Tru Age OMICm Age test results.	To see if any pattern exists within age group categories. (50-65; older than age 65). Change in OMICm methylation results from baseline to Week 24 by two sub populations: ages 50-65 and ages older than age 65	24 weeks
Sex Difference based on Tru Diagnostic Tru Age OMICm Age test results.	Change in OMICm methylation from baseline to Week 24 by male vs female	24 weeks
Safety and tolerability of rapamycin and Prolon	Review of adverse reactions from baseline to Week 28	28 weeks

Collaborators and Investigators

• Sponsor: The Christ Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 21, 2026

Study Record Updates

• Last Update Posted (Actual): January 21, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Aging; Rapamycin; Biological Age; Reverse Aging; Chronological Age; Prolon
• Additional Relevant MeSH Terms: Organic Chemicals; Pharmaceutical Preparations; Dosage Forms; Macrolides; Lactones; Sirolimus; Tablets
• Other Study ID Numbers: 24-088

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes