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The Role of Sirolimus in Preventing Functional Decline in Older Adults

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ClinicalTrials.gov Identifier: NCT05237687
Recruitment Status : Not yet recruiting
First Posted : February 14, 2022
Last Update Posted : November 4, 2022
Sponsor:
Information provided by (Responsible Party):
Irina Timofte, University of Texas Southwestern Medical Center

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.


Condition or disease Intervention/treatment Phase
Aging Drug: Sirolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: The Role of Sirolimus in Preventing Functional Decline in Older Adults
Estimated Study Start Date : December 2022
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Sirolimus

Arm Intervention/treatment
Active Comparator: Intervention
Patients randomized to the intervention will initially take 0.5 mg sirolimus. The dose will be adjusted weekly to obtain a sirolimus levels of 5-7 ng/ml whole blood in the first months. After the first month, the patient will have monthly blood work and will be followed in clinic every 3 months. Functional assessment and aging biomarkers will be obtained at baseline and 1 year follow up. Completion of the 1-year treatment period will be followed by a follow-up visit 4 weeks later.
Drug: Sirolimus
Patients will be randomly assigned to sirolimus or standard of care

No Intervention: Control
Interventions: standard of care Patients are not going to receive any additional intervention.



Primary Outcome Measures :
  1. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by walking speed

  2. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by chair stand

  3. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by standing balance

  4. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by grip strength

  5. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by body mass index

  6. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by muscle mass

  7. Phenotypic/functional biomarkers of aging [ Time Frame: 1 year ]
    Phenotypic/functional biomarkers of aging as measured by waist circumference


Secondary Outcome Measures :
  1. Circulating biomarkers of aging as measured by ESR [ Time Frame: 1 year ]
    We are going to check circulating biomarkers of aging as measured by erythrocyte sedimentation rate(ESR)

  2. Circulating biomarkers of aging as measured by C-reactive protein(CRP) [ Time Frame: 1 year ]
    We are going to check circulating biomarkers of aging as measured by C-reactive protein(CRP)

  3. Circulating biomarkers of aging as measured by levels of Hemoglobin(Hb) [ Time Frame: 1 year ]
    We are going to check circulating biomarkers of aging as measured by levels of Hemoglobin(Hb)



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • patients 55 years or older

Exclusion Criteria:

  • 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)
  • Patients not able to understand or follow trial procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05237687


Contacts
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Contact: Irina Timofte 2163347534 Irina.Timofte@utsouthwestern.edu

Sponsors and Collaborators
University of Texas Southwestern Medical Center
Publications:
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Responsible Party: Irina Timofte, ASSOC PROFESSOR, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT05237687    
Other Study ID Numbers: STU-2022-0060
First Posted: February 14, 2022    Key Record Dates
Last Update Posted: November 4, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Irina Timofte, University of Texas Southwestern Medical Center:
aging
sirolimus
prevention
Additional relevant MeSH terms:
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Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs