RESTOR: PK/PD mTORi Inhibition in Older Adults
ConditionAging
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age65-90
SponsorThe University of Texas Health Science Center at San Antonio
About this trial
As people get older, there are changes in their cells and tissues that may affect their ability to function. This can lead to increased death and age-associated disorders, like heart disease, cancer, and Alzheimer's disease. Studies in animal models have been able to identify drugs that slow the aging process, leading to a longer, healthier life. This study is focused on one such family of drugs, called mTOR inhibitors, and the investigators' goal is to test two of these drugs, Rapamycin (Sirolimus) and Everolimus (Afinitor), in healthy older adults to find a dose and dose timing that can be used to safely inhibit mTOR to the levels seen in young healthy persons. The investigators expect that the dose that works well in women may differ from the one that is best in men, so it is important to include both sexes in this research.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age ≥65 to 90 years
Men and women
In good health with all medical problems stable.
Community-dwelling
Disqualifiers
Resident of nursing home or long-term care facility
Subjects with diabetes or currently taking glucose lowering medications
History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation); Moderate to severe valvular heart disease
Active cancer or history of cancer treatment within the last 5 years
Trial design
Design model
Sequential
Treatments tested in this trial
Rapamycin
DrugmTOR inhibitor
Everolimus
DrugmTOR inhibitor
Placebo
Other interventionInert placebo for rapamycin or everolimus
Treatment groups
194 Participants
are divided into 7 treatment groups7
Treatment groupsSee each treatment group below.
Group A: Aim 1:Sub-study 2 Daily dosing Cohort RapamycinExperimental treatment 1 intervention
Group B: Aim 1: Sub-study 2 Daily dosing Cohort EverolimusExperimental treatment 1 intervention
Group C: Aim 1:Sub-study 2 Intermittent dosing Cohort RapamycinExperimental treatment 1 intervention
Group D: Aim 1: Sub-study 2 Intermittent dosing Cohort EverolimusExperimental treatment 1 intervention
Group E: Aim 2: Sub-study 3 Optimized DAILY Dose of an mTOR inhibitorExperimental treatment 2 interventions
Group F: Aim 2: Sub-study 3 Optimized INTERMITTENT Dosing of an mTOR inhibitorExperimental treatment 2 interventions
Group G: Aim 2: Sub-study 3 Placebo controlPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Pharmacokinetics (PK) of mTOR inhibitor in blood
The levels of the study drug will be measured in whole blood
Time frame
Baseline to study end (approximately 12 months for Aim 2; 12 weeks for Aim 1)2
PD measure of inhibition of mTOR activity in blood cells - p-rpS6
Proteins prepared from PBMCs (peripheral blood mononuclear cells) will be analyzed for phosphorylation of ribosomal protein S6, downstream of mTORC1.
Time frame
Baseline to study end (approximately 12 months for Aim 2; 12 weeks for Aim 1)3
Level of Soluble Intercellular Adhesion Molecule-1 (sICAM-1)
The level of soluble (s)ICAM-1 will be measured in serum.
Time frame
Baseline to study end (approximately 12 months)Secondary outcomes
1
PK of mTOR inhibitor in fat (Aim 2 only)
The levels of the study drug will be measure in fat tissue obtained by adipose biopsy
Time frame
Baseline and study end (approximately 12 months)2
PK of mTOR inhibitor in muscle (Aim 2 only)
The levels of the study drug will be measured in skeletal muscle obtained by biopsy.
Time frame
Baseline to study end (approximately 12 months)3
PD measure of inhibition of mTOR activity in fat cells (Aim 2 only) - pS6K
Proteins prepared from adipose tissue will be analyzed for phosphorylation of S6kinase, downstream of mTORC1.
Time frame
Baseline to study end (approximately 12 months)4
PD measure of inhibition of mTOR activity in muscle (Aim 2 only) - pS6K
Proteins prepared from skeletal muscle tissue biopsy will be analyzed for phosphorylation of S6kinase, downstream of mTORC1.
Time frame
Baseline to study end (approximately 12 months)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
The University of Texas Health Science Center at San Antonio
Lead sponsor
National Institute on Aging (NIA)
Collaborator
Source ClinicalTrials.gov