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

Primary Purpose

Aging, Epigenetics, Inflammatory Mediators

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rapamycin Topical Ointment
Placebo
Sponsored by
The University of Texas Health Science Center at San Antonio
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aging focused on measuring Epigenetic clock

Eligibility Criteria

65 Years - 95 Years (Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • UTHSCSA

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Topical Rapamycin

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
October 21, 2020
Last Updated
June 26, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT04608448
Brief Title
Topical-RAPA Use in Inflammation Reversal and Re-setting the Epigenetic Clock
Acronym
Topical-RAPA
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 28, 2021 (Actual)
Primary Completion Date
April 15, 2022 (Actual)
Study Completion Date
April 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
Collaborators
National Institute on Aging (NIA)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aging, Epigenetics, Inflammatory Mediators
Keywords
Epigenetic clock

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Participants will be their own control, either right or left arm will be randomized to treatment or placebo.
Masking
ParticipantInvestigator
Masking Description
Randomization will be performed by the compounding pharmacy. Ointment dispensers will be color-coded for left and right arm for each subject.
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topical Rapamycin
Arm Type
Active Comparator
Arm Description
Ointment is applied to a color coded area on the subject forearm daily.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo ointment is applied to a color coded area on the subject forearm daily.
Intervention Type
Drug
Intervention Name(s)
Rapamycin Topical Ointment
Other Intervention Name(s)
Sirolimus Topical Ointment, RAPA Topical Ointment
Intervention Description
8% topical rapamycin ointment
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Topical Ointment, Petrolatum
Intervention Description
Petrolatum ointment containing no active ingredient
Primary Outcome Measure Information:
Title
Change in Epigenetic Markers
Description
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.
Time Frame
Baseline to 6 months
Secondary Outcome Measure Information:
Title
Change in Inflammatory Marker IL-6
Description
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.
Time Frame
Baseline to 6 months
Title
Change in Inflammatory Marker CRP
Description
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.
Time Frame
Baseline to 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ellen Kraig, PhD
Organizational Affiliation
University of Texas Health at San Antonio
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dean L Kellogg, Jr., MD, PhD
Organizational Affiliation
University of Texas Health at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
UTHSCSA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78220
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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