Trial Outcomes & Findings for Topical-RAPA Use in Inflammation Reversal and Re-setting the Epigenetic Clock (NCT NCT04608448)

Last Updated: 2023-07-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Baseline to 6 months

Results posted on

2023-07-19

Participant Flow

Subjects acted as their own controls, one forearm had rapamycin ointment applied and the other placebo, thus there were 20 participants who had both rapamycin applied to one arm and placebo to the other.

Unit of analysis: Forearms of subjects

Participant milestones

Participant milestones
Measure	Topical Rapamycin Applied to One Arm and Placebo Applied to the Opposite Arm Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment
Overall Study STARTED	22 44
Overall Study COMPLETED	20 40
Overall Study NOT COMPLETED	2 4

Reasons for withdrawal

Reasons for withdrawal
Measure	Topical Rapamycin Applied to One Arm and Placebo Applied to the Opposite Arm Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

Each subject applied either an ointment containing the mTOR inhibitor rapamycin or a vehicle-only control ointment to a 1 cm patch of skin on the forearm daily for 6 months.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Topical Rapamycin n=20 Participants Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment to one arm and Petrolatum ointment containing no active ingredient to the opposite arm
Age, Customized Age 65-92 years	20 Participants n=5 Participants • Each subject applied either an ointment containing the mTOR inhibitor rapamycin or a vehicle-only control ointment to a 1 cm patch of skin on the forearm daily for 6 months.
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 6 months

Population: DNA prepared from the placebo and rapamycin-treated skin sites was analyzed for methylation at specific sites known to change with age.

Outcome measures

Outcome measures
Measure	Topical Rapamycin n=20 Forearm of participant Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment	Placebo n=20 Forearm of participant Placebo ointment is applied to a color coded area on the subject forearm daily. Placebo: Petrolatum ointment containing no active ingredient
Change in Epigenetic Markers	84.4 years Interval 66.2 to 109.8	82.8 years Interval 64.3 to 98.1

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: Recovery of blister fluid from some subjects was lower than anticipated so a Luminex-based array assay, which uses much lower sample volumes than ELISAs, was performed and the cytokine levels on the rapamycin treated side were compared to the placebo levels.

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.

Outcome measures

Outcome measures
Measure	Topical Rapamycin n=16 Blisters Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment	Placebo n=16 Blisters Placebo ointment is applied to a color coded area on the subject forearm daily. Placebo: Petrolatum ointment containing no active ingredient
Change in Inflammatory Marker IL-6	1.44 pg/ml Interval 0.0 to 11.74	1.57 pg/ml Interval 0.0 to 7.97

SECONDARY outcome

Timeframe: Baseline to 6 months

Outcome measures

Outcome data not reported

Adverse Events

Topical Rapamycin

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Topical Rapamycin n=22 participants at risk Ointment is applied to a color coded area on the subject forearm daily. Rapamycin Topical Ointment: 8% topical rapamycin ointment	Placebo n=22 participants at risk Placebo ointment is applied to a color coded area on the subjects' opposite forearm daily.
Skin and subcutaneous tissue disorders Rash/redness	18.2% 4/22 • Number of events 4 • Adverse events were collected from baseline to 6 months Adverse events are reported per subject arm, since each subject had both rapamycin applied to one arm and placebo to the other arm	18.2% 4/22 • Number of events 4 • Adverse events were collected from baseline to 6 months Adverse events are reported per subject arm, since each subject had both rapamycin applied to one arm and placebo to the other arm

Additional Information

Ellen Kraig, PhD

UT Health San Antonio

Phone: 210-567-3818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place