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

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

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

Study Overview

• Status: Completed
• Conditions: Aging; Epigenetics; Inflammatory Mediators
• Intervention / Treatment: Drug: Rapamycin Topical Ointment; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78220
      • UTHSCSA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 95 years (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Ellen Kraig, PhD, University of Texas Health at San Antonio; Principal Investigator: Dean L Kellogg, Jr., MD, PhD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Actual): April 15, 2022
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 27, 2020
• First Posted (Actual): October 29, 2020

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Epigenetic clock
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Emollients; Sirolimus; Petrolatum
• Other Study ID Numbers: HSC20200720H; 1R21AG068731-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Unidentified IPD will be shared in publication form in peer-reviewed journals, at national or international meetings and with collaborating investigators at the PIs home institution.

Summary results will be published on ClinicalTrials.gov.

• IPD Sharing Time Frame: Data will be shared upon study completion.
• IPD Sharing Access Criteria: Will be provided upon formal request to PI and/or included in publications.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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.: No