The Role of Sirolimus in Preventing Functional Decline in Older Adults

NCT05237687 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU-2023-0909
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Aging is associated with progressive impairment of tissue and organ function, resulting in increased susceptibility to chronic disease, frailty and disability. Currently there are limited treatment options to alter this inevitable process. The proposed work has the potential to identify a new therapeutic intervention to decrease aging-related degenerative processes. Rapamycin or sirolimus is a macrocyclic immunosuppressive drug that inhibits the mammalian target of rapamycin (mTOR). The mammalian target of rapamycin (mTOR) pathway is part of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway which is a fundamentally linked to cell metabolism, proliferation, differentiation, and survival. This pathway is altered in a variety of diseases, including cancers, immunosuppressed states, and fibroproliferative diseases. The mTOR kinase is considered one of the leading regulators of this pathway. Changes in mTOR signaling are closely associated with inflammation, cell growth and survival, leading to the development of chronic diseases. Recent evidence also suggests that mTOR inhibitors are promising modulators of the aging process by slowing the mechanisms of aging at the cellular level. There is a growing appreciation of the potential impact of sirolimus in slowing aging processes and in prolonging healthy lifespan. The proposed study addresses critical gaps in our understanding of the safety and efficacy of sirolimus in delaying aging processes and is based on findings in animal studies and incidental clinical observations. The investigators will overcome potential biases with a randomized control trial. The proposed intervention study is intended to improve our insight into clinical outcomes leading to prevention of chronic diseases such as skin cancer and mortality. Our overarching hypothesis is that sirolimus is one of the first pharmacological agents that will impact the aging process and chronic disease development. Specifically, the investigators aim to investigate whether sirolimus can reduce the occurrence or increase in biomarkers of aging processes.

Conditions

Aging

Keywords

aging; sirolimus; prevention

Outcome Measures

Primary Outcomes (1)

• Phenotypic/functional biomarkers of aging

  Phenotypic biomarkers of aging will be measured by SASP (senescence-associated secretory phenotype) index score at 1 year follow-up when compared to elderly patients not receiving sirolimus.

  1 year

Secondary Outcomes (5)

• Phenotypic/functional biomarkers of aging

  1 year

• Phenotypic/functional biomarkers of aging

  1 year

• Phenotypic/functional biomarkers of aging

  1 year

• Phenotypic/functional biomarkers of aging

  1 year

• Feasibility of collecting the laboratory biomarkers and analyzing the data regarding annual rate of decline in functional biomarkers of aging

  1 year

Study Arms (2)

Intervention

EXPERIMENTAL

Patients will be randomized using age-based randomization to initial treatment with 0.5 mg sirolimus p.o. (orally) everyday vs standard of care. The medications would be dispensed from UT Southwestern Medical Center. To ensure patent's safety, all patients will be closely monitored. We will start with a 0.5 mg tablet- the smallest sirolimus dose available. Sirolimus level will be checked weekly in the first month to ensure we maintain a low goal (5-7) that will decrease the risk of developing side effects. In order to monitor study drug compliance, we will ask the patient to keep a pill diary. After the first month, the patient will have monthly blood work and monthly phone call to enquire about potential side effects. The patients will be followed in clinic in person every 3 months. Functional assessment will be obtained at baseline, 3 months 6 months 9 months and 1 year follow up. Completion of the 1-year treatment period will be followed by a follow-up phone call 1 month later.

Drug: Sirolimus

Control

NO INTERVENTION

Interventions: standard of care Patients are not going to receive any additional intervention.

Interventions

Sirolimus DRUG

Patients will be randomly assigned to sirolimus or standard of care

Intervention

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients should be adults 65-80 years
• Women who are postmenopausal\* or status post-surgical sterilization only
• Competent to provide Informed Consent

You may not qualify if:

• Creatinine clearance \<30 mL/min
• Underlying chronic liver disease
• Other investigational therapy received within 1 month prior to screening visit
• Pulmonary Arterial Hypertension (PAH), mean Pulmonary Arterial Presure(mPAP)\>30 mm Hg
• Extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)
• Cardiovascular diseases, any of the following: Myocardial infarction within 6 months, planned coronary artery disease intervention , left ventricular EF \<45%
• History of haemorrhagic central nervous system (CNS) event within 1 year from screening visit.
• Any of the following within 3 months of screening visit :Haemoptysis or haematuria;Active gastro-intestinal (GI) bleeding or GI - ulcers; Major injury or surgery
• History of thrombotic event (including, DVT, PE, stroke and transient ischemic attack) within 1 year from screening visit.
• Other disease that may interfere with testing procedures or in the judgment of the Investigator may interfere with trial participation or may put the patient at risk when participating in this trial.
• Planned major surgical procedures.
• Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
• Concurrent active alcohol or drug abuse.
• Clinically significant cognitive impairment
• Functional impairment (defined by ADL status)

Sponsors & Collaborators

• Irina Timofte: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

Related Publications (3)

• Lamming DW, Ye L, Sabatini DM, Baur JA. Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest. 2013 Mar;123(3):980-9. doi: 10.1172/JCI64099. Epub 2013 Mar 1.

  PMID: 23454761 BACKGROUND

• Hsu HS, Liu CC, Lin JH, Hsu TW, Hsu JW, Su K, Hung SC. Involvement of ER stress, PI3K/AKT activation, and lung fibroblast proliferation in bleomycin-induced pulmonary fibrosis. Sci Rep. 2017 Oct 27;7(1):14272. doi: 10.1038/s41598-017-14612-5.

  PMID: 29079731 BACKGROUND

• Lawrence J, Nho R. The Role of the Mammalian Target of Rapamycin (mTOR) in Pulmonary Fibrosis. Int J Mol Sci. 2018 Mar 8;19(3):778. doi: 10.3390/ijms19030778.

  PMID: 29518028 BACKGROUND

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Irina Timofte, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irina Timofte

CONTACT

2163347534; Irina.Timofte@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 19, 2022
• First Posted: February 14, 2022
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)