Topical-RAPA Use in Inflammation Reversal and Re-setting the Epigenetic Clock

Early Phase 1

Completed

Brief Summary: Topical Rapamycin ointment will be applied to participant forearms to test whether epigenetic changes in the skin are elicited.

Detailed Description: Rapamycin 8% ointment will be applied topically to one of the participant's forearms and matching placebo to the opposite forearm daily for a total of 6 months. After consenting, screening and randomization of arms, the participants will be monitored at monthly visits until study completion.

Recruitment & Eligibility

Inclusion Criteria

65-95 years of age.
Good health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable.
Selected subjects will be in good health (Per the World Health Organization, good health will be defined as complete physical, mental, and social well-being and not merely the absence of disease or infirmity).
All diseases or infirmities will be clinically stable whether managed by medications or not.
CLOX score of 10 or greater
Women will be postmenopausal
Postmenopausal women taking hormone replacement will be included if they have been on a stable dose for ≥6 months
Live within a 20 mile drive of the UTHSA campus (7703 Floyd Curl Drive, San Antonio, TX)

Exclusion Criteria

Diabetes.
History of skin ulcers or poor wound healing, or keloid formers.
Smoking.
Liver disease.
Coumadin anti-coagulation.
Treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin, etc. - due to role in rapamycin metabolism).
Treatment with an immunosuppressant (prednisone, etc.) within 6 months.
History of recent (within 6 months) Myocardial Infarction or active Coronary Disease.
Hypersensitivity to rapamycin or petrolatum (ointment vehicle)
Arm tattoos or scars in application area

Arm && Interventions

Group	Intervention	Description
Topical Rapamycin	Rapamycin Topical Ointment	Ointment is applied to a color coded area on the subject forearm daily.
Placebo	Placebo	Placebo ointment is applied to a color coded area on the subject forearm daily.

Primary Outcome Measures

Name	Time	Method
Change in Epigenetic Markers	Baseline to 6 months	A set of DNA methylation marks that correlate with chronological age will be used to measure rejuvenation of the "epigenetic clock" due to drug treatment compared to placebo. Using Illumina EPIC arrays, CpG methylation will be assessed and then the predicted age, based on the combined methylation at the set of 391 marks (the "epigenetic clock" as defined by Dr. Steven Horvath, UCLA), will be determined.

Secondary Outcome Measures

Name	Time	Method
Change in Inflammatory Marker IL-6	Baseline to 6 months	A measure of inflammatory markers will include analytes that are affected either by aging or oral rapamycin. Inflammatory markers are measured using Enzyme-Linked Immuno-Sorbant Assays (ELISA). The marker to be measured is IL-6.
Change in Inflammatory Marker CRP	Baseline to 6 months	A measure of inflammatory markers will include analytes that are affected either by aging or oral rapamycin. Inflammatory markers are measured using Enzyme-Linked Immuno-Sorbant Assays (ELISA). The marker to be measured is CRP. No data were obtained from this measure due to the low blister fluid volume.