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

Study Overview
=================
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.

Official Title
-----------------
An Innovative Proof-of-concept Approach to Identify Age-modulating Drugs Capable of Reversing Inflammation and Re-setting the Epigenetic Clock (Topical-RAPA)

Conditions
-----------------
Aging, Epigenetics, Inflammatory Mediators

Intervention / Treatment
-----------------
* Drug: Rapamycin Topical Ointment
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be their own control, either right or left arm will be randomized to treatment or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Topical Rapamycin<br>Ointment is applied to a color coded area on the subject forearm daily. | Drug: Rapamycin Topical Ointment<br>* 8% topical rapamycin ointment<br>* Other names: RAPA Topical Ointment;|
| Placebo Comparator: Placebo<br>Placebo ointment is applied to a color coded area on the subject forearm daily. | Other: Placebo<br>* Petrolatum ointment containing no active ingredient<br>* Other names: Petrolatum;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epigenetic Markers | 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. | Baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Inflammatory Marker IL-6 | 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. | Baseline to 6 months | 
| Change in Inflammatory Marker CRP | 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. | Baseline to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Epigenetic clock