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

NCT04608448 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: HSC20200720H1R21AG068731-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Aging; Epigenetics; Inflammatory Mediators

Keywords

Epigenetic clock

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change in Inflammatory Marker IL-6

  Baseline to 6 months

• Change in Inflammatory Marker CRP

  Baseline to 6 months

Study Arms (2)

Topical Rapamycin

ACTIVE COMPARATOR

Ointment is applied to a color coded area on the subject forearm daily.

Drug: Rapamycin Topical Ointment

Placebo

PLACEBO COMPARATOR

Placebo ointment is applied to a color coded area on the subject forearm daily.

Other: Placebo

Interventions

Rapamycin Topical Ointment DRUG

8% topical rapamycin ointment

Also known as: Sirolimus Topical Ointment, RAPA Topical Ointment

Topical Rapamycin

Placebo OTHER

Petrolatum ointment containing no active ingredient

Also known as: Placebo Topical Ointment, Petrolatum

Placebo

Eligibility Criteria

• Age: 65 Years - 95 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

UTHSCSA

San Antonio, Texas, 78220, United States

Location

MeSH Terms

Interventions

Petrolatum

Intervention Hierarchy (Ancestors)

Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Ellen Kraig, PhD
• Organization: UT Health San Antonio

kraig@uthscsa.edu

210-567-3818

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomization will be performed by the compounding pharmacy. Ointment dispensers will be color-coded for left and right arm for each subject.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof & Deputy Chair of Faculty Development Cell Systems & Anatomy

Model Details: Participants will be their own control, either right or left arm will be randomized to treatment or placebo.

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: October 29, 2020
• Study Start: April 28, 2021
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: July 19, 2023
• Results First Posted: July 19, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared upon study completion.
• Access Criteria: Will be provided upon formal request to PI and/or included in publications.

Locations

US (1)