AzTrials
AzTrials

AgingEarly Phase 1RESTORNCT06658093

RESTOR: PK/PD mTORi Inhibition in Older Adults

A Early Phase 1 study testing Rapamycin and Everolimus in people with Aging, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 65 to 90 yearsHealthy volunteers can take part
Conditions the study is for
Aging
What is being tested?
Rapamycin and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
194 participants
Where
1 siteUnited States
Study dates
4 Mar 2026to Jul 2028
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
  • Age ≥65 to 90 years
  • Men and women
  • In good health with all medical problems stable.
  • Community-dwelling
  • Agreement to adhere to Lifestyle Considerations throughout study duration.
  • Ability of participant to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Older Cohort Sub-study 2 (AIM 1) and Sub-study 3 (AIM 2):
  • 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
  • Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, HIV, rheumatoid arthritis, systemic lupus erythematosus, acute or chronic hepatitis B or C)
Show all 29Show fewer
  • History of a coagulopathy or any medical condition requiring anticoagulation (except low dose ASA)
  • Renal insufficiency with an estimated glomerular filtration rate of <30ml/min
  • Uncontrolled hypercholesterolemia >350mg/dl or uncontrolled hypertriglyceridemia >500mg/dl
  • Anemia or abnormal blood cell counts: hemoglobin level <9.0g.dl; white blood count <3500/mm3; neutrophil count <2000/ mm3; platelet count <125,000/mm3
  • History of skin ulcers or poor wound healing
  • Active tobacco use (within 6 months)
  • Diagnosis of any disabling neurologic disease such as Parkinson's Disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (muscle weakness or gait disorder), severe neuropathy, diagnosis of dementia or Clox1 score less than 10 at the time of screening visit, cognitive impairment due to any reason such that the patient is unable to provide informed consent
  • Liver disease
  • Systemic treatment with an immunosuppressant (prednisone, etc.) within the year prior to enrollment
  • Treatment with drugs known to affect cytochrome P450 (CYP3A4), i.e., diltiazem, erythromycin.
  • Patients with history of recent (within 6 months) myocardial infarction or active coronary disease
  • Patients with history of recent (within 6 months) intestinal disorders
  • History of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizure disorder
  • History of Long-Covid (PASC) within one year
  • Acute Covid19 or Covid19 infection within the last 6 months
  • Unwilling to forgo grapefruit juice consumption.
  • Participation in mTORi study within the prior year. (Note: participants in AIM 1 will be excluded from participating in AIM 2 of the proposed trial.)
  • Allergic to RAPA or EVERO
  • Allergic to lidocaine
  • Recreational drug use
  • Donated blood over a two-month period prior to study initiation.
  • Currently using cannabidiol (CBD) or tetrahydrocannabinol (THC) or any preparation contained these, or related, substances.
  • Currently using hormone replacement or modulating therapies.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Dean L Kellogg, Jr, MD PhD contact

(210) 617 5197

kelloggd@uthscsa.edu

Ellen Kraig, PhD contact

(210) 367-3171

kraig@uthscsa.edu

United States1 site, 1 recruiting

  • The University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

    Dean L Kellogg Jr.,, MD PhD, 210-617-5197, kelloggd@uthscsa.edu

    Dean L Kellogg Jr., MD PhD

    Recruiting

Other trials in United States

About this study

Official title: RESTOR [Rapamycin and Everolimus Study Towards Older Rejuvenation]: An Exploratory PK/PD Study of mTOR Inhibition in Older Human Subjects

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.

Read the detailed description

The study will be done in three parts, each with different human subject groups. Participants may only enroll in one of the sub-studies.

Sub-study 1: Determining target mTOR activity values in YOUNG untreated subjects (ages 20-30 years): NOTE: This aim of the study is not a clinical trial, so this population will not be included in participant flow or included as an arm in the study.

This study defines "best dose" as the choice of drug, dose, and frequency that will come closest to restoring the "youthful" levels of mTOR activity in an older individual. The investigators first need to measure mTOR activity in young untreated subjects to define these target "youthful" mTOR activity levels.

Sub-study 2. Finding the most effective drug, dose, and timing for dosing for oral dosing of the mTOR inhibitor drugs in older adults (65-90 years):

Healthy older persons will be recruited for a short-term (6 week treatment plus 4 week follow-up) dose-finding study. The most effective, but safe dose will then be tested in a larger number of subjects in Sub-study 3. Importantly, the best drug and dose regimen for females may differ from the one determined for males so the cohort will include both sexes.

Sub-study 3. Placebo controlled trial testing of DAILY (sustained) vs. INTERMITTENT mTOR inhibition in older human males and females:

Sub-study 3 will enroll healthy older persons (65-90 yrs) for a long-term clinical trial (6 months of treatment plus 6 months of follow-up) with 3 test groups:

  1. best DAILY dose/drug; ii) best INTERMITTENT dose/drug/interval, and iii) PLACEBO (a pill that looks identical to the medicine, but has no drug in it).

This study will help find out what effects, good and/or bad, Rapamycin or Everolimus have on older people who take the drug for a longer period of time. The safety of Rapamycin and Everolimus in humans has been tested in prior research studies; however, some side effects may not yet be known in healthy older persons. By completing the entire study, the Research Team hopes to learn more about how older human subjects can best be treated using these drugs (mTOR inhibitors) to help them live longer, healthier lives.

Conditions
Aging
Being tested
Rapamycin, Everolimus, Placebo
Keywords
mTOR inhibitors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RapamycinDrug

    Also called RAPA

    mTOR inhibitor

  • EverolimusDrug

    Also called EVERO

    mTOR inhibitor

  • PlaceboOther

    Also called Placebo capsule

    Inert placebo for rapamycin or everolimus

Study groups in NCT06658093
Study groupRoleWhat they receive
Aim 1:Sub-study 2 Daily dosing Cohort RapamycinExperimentalAim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams of rapamycin (RAPA) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.
Receives: Drug: Rapamycin
Aim 1: Sub-study 2 Daily dosing Cohort EverolimusExperimentalAim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) of everolimus (EVERO) in milligrams based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.
Receives: Drug: Everolimus
Aim 1:Sub-study 2 Intermittent dosing Cohort RapamycinExperimentalAim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams and the optimal interval for intermittent delivery of rapamycin (RAPA) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.
Receives: Drug: Rapamycin
Aim 1: Sub-study 2 Intermittent dosing Cohort EverolimusExperimentalAim 1 is an open label, adaptive, dose finding PK/PD trial in older women and men. In sub-study 2 (part of Aim 1), an older cohort will be studied to determine the optimal dose (OD) in milligrams and the optimal interval for intermittent delivery of everolimus (EVERO) based on changes in PD parameters 'downstream' from mTOR. Based on the data acquired, additional older cohorts will be tested at higher/lower doses in an adaptive, step-wise trial design.
Receives: Drug: Everolimus
Aim 2: Sub-study 3 Optimized DAILY Dose of an mTOR inhibitorExperimentalBased on the findings from Aim 1, the optimal drug (RAPA or EVERO) and dose for DAILY delivery will be tested in a blinded placebo-controlled trial in older human subjects. The drug/dose used in males may differ from the one used in females as the OD will be determined independently for the two sexes. PD parameters 'downstream' from mTOR will be followed.
Receives: Drug: Rapamycin; Drug: Everolimus
Aim 2: Sub-study 3 Optimized INTERMITTENT Dosing of an mTOR inhibitorExperimentalBased on the findings from Aim 1, the optimal drug (RAPA or EVERO), interval between doses, and dose for INTERMITTENT delivery will be tested in a blinded placebo-controlled trial in older human subjects. The drug/dose/interval used in males may differ from the one used in females as the OD will be determined independently for the two sexes. PD parameters 'downstream' from mTOR will be followed. Although drug is delivered on an intermittent schedule, subjects will be given a pill each day (either drug or placebo, as scheduled) to maintain blinding.
Receives: Drug: Rapamycin; Drug: Everolimus
Aim 2: Sub-study 3 Placebo controlPlacebo comparatorDaily administration of a placebo will be given to a cohort of older human subjects. Both males and females will be enrolled as controls.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics (PK) of mTOR inhibitor in blood

    The levels of the study drug will be measured in whole blood

    Measured: 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.

    Measured: 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.

    Measured: Baseline to study end (approximately 12 months)

Secondary outcomes (10)

  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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: Baseline to study end (approximately 12 months)

  5. PD measure of inhibition of mTOR activity in PBMCs, S6-kinase

    Proteins prepared from PBMCs (peripheral blood mononuclear cells) will be analyzed for phosphorylation of S6kinase, downstream of mTORC1.

    Measured: Baseline to study end (approximately 12 months)

  6. PD measure of inhibition of mTOR activity in adipose cells, rpS6 (Aim 2 only)

    Proteins prepared from adipose biopsies will be analyzed for phosphorylation of ribosomal protein S6, downstream of mTORC1.

    Measured: Baseline to study end (approximately 12 months)

  7. PD measure of inhibition of mTOR activity in muscle rpS6 (Aim 2 only)

    Proteins prepared from muscle biopsies will be analyzed for phosphorylation of ribosomal protein S6, downstream of mTORC1.

    Measured: Baseline to study end (approximately 12 months)

  8. PD measure of inhibition of mTOR activity in adipose (fat) cells Akt (Aim 2 only)

    Proteins prepared from adipose biopsies will be analyzed for phosphorylation of Akt, downstream of mTORC2.

    Measured: Baseline to study end (approximately 12 months)

  9. PD measure of inhibition of mTOR activity in muscle Akt (Aim 2 only)

    Proteins prepared from muscle biopsies will be analyzed for phosphorylation of Akt, downstream of mTORC2.

    Measured: Baseline to study end (approximately 12 months)

  10. PD measure of inhibition of mTOR activity in PBMCs Akt

    Proteins prepared from PBMCs will be analyzed for phosphorylation of Akt, downstream of mTORC2.

    Measured: Baseline to study end (approximately 12 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2024
  2. Study start4 Mar 2026
  3. Primary completionJul 2028 (estimated)
  4. Study completionJul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Sequential
Model description
A single site open label adaptive clinical trial (Aim 1:Sub-study 2) followed by a placebo-controlled blinded clinical trial (Aim 2) to optimize the use of mTOR inhibitors in older persons a functions of drug, dose, dosing schedule and sex. It will be carried out in 2 sub-studies: Aim 1: -Sub-study 2: Comparison of 2 mTOR inhibitors in an adaptive open-label dose finding pharmacokinetic/pharmacodynamic study Aim 2: Sub-study 3: Assess the safety/tolerability/adverse events of optimized dose of mTOR inhibitors in daily vs intermittent dosing
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
194 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06658093
Sponsor's protocol ID
STUDY00000471
Other IDs
U01AG089242
Acronym
RESTOR
Status last verified
May 2026
First submitted
22 Oct 2024
Last updated
1 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified Individual participant data (IPD) that underlie results in a publication.

Publications

  • Kraig E, Linehan LA, Liang H, Romo TQ, Liu Q, Wu Y, Benavides AD, Curiel TJ, Javors MA, Musi N, Chiodo L, Koek W, Gelfond JAL, Kellogg DL Jr. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects. Exp Gerontol. 2018 May;105:53-69. doi: 10.1016/j.exger.2017.12.026. Epub 2018 Feb 3.

    PubMed 29408453

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Rapamycin and Everolimus in people with Aging, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Dean L Kellogg, Jr, MD PhD ((210) 617 5197, kelloggd@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics (PK) of mTOR inhibitor in blood (time frame: Baseline to study end (approximately 12 months for Aim 2; 12 weeks for Aim 1)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06658093, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in