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Effect of mTOR Inhibition & Other Metabolism Modulating Interventions on the Elderly [SubStudy Rapa & cMRI to Evaluate Cardiac Function] (mTOR)

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ClinicalTrials.gov Identifier: NCT04742777
Recruitment Status : Recruiting
First Posted : February 8, 2021
Last Update Posted : May 25, 2022
Sponsor:
Collaborators:
The Claude D. Pepper Older Americans Independence Centers
National Institute on Aging (NIA)
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Brief Summary:

The ability to mount an effective immune response declines with age, leaving the elderly increasingly susceptible to infectious diseases and cancer. Rapamycin, an FDA approved drug to prevent transplant rejection, increases the lifespan and healthspan of mice and ameliorates age-related declines in immune responsiveness, cancer survival, and cognition in laboratory animals. Investigators are conducting a translational trial to test whether rapamycin also improves life functions in humans focusing on elderly persons (aged 70-95).

Substudy E will evaluate the Rapamycin and Cardiac Function.


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

Detailed Description:

The main study has completed and results are reported (NCT02874924)

Purpose of Sub-study E - Rapamycin and cMRI to evaluate cardiac function:

The over-arching hypothesis is that RAPA treatment will effect simultaneous improvement in parameters known to be negatively impacted by aging. For example, systemic inflammation is higher in older individuals and contributes to the development of age-related pathologies affecting both the heart and the vasculature. In particular, evidence indicates that aging-associated alterations in inflammatory and pro-fibrotic pathways are critically involved in the etiology of age-related declines. The study team hypothesize that mTOR antagonism with RAPA will improve detrimental age-related pathologies affecting the heart in elderly humans.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Rapamycin 1mg for 8 weeks
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effect of mTOR Inhibition and Other Metabolism Modulating Interventions on the Elderly: Immune, Cognitive, and Functional Consequences ((Substudy E - RAPA cMRI With LGE)
Actual Study Start Date : February 1, 2022
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Rapamycin
Rapamycin 1mg for 8 weeks
Drug: rapamycin
Taken orally 1mg daily for 8 weeks
Other Name: Sirolimus




Primary Outcome Measures :
  1. Systolic Function [ Time Frame: Baseline to 8 weeks ]
    Test whether RAPA improves systolic function in elderly subjects. Cardiac MRI will be measured before and after 8 weeks of RAPA administration using 3T MRI. From collected MRI data, the study team will quantify change in systolic volumes.

  2. Diastolic Function [ Time Frame: Baseline to 8 weeks ]
    Test whether RAPA improves diastolic function in elderly subjects.Cardiac MRI will be measured before and after 8 weeks of RAPA administration using 3T MRI. From collected MRI data, the study team will quantify change in diastolic volumes.

  3. Aortic Cross-Sectional Area [ Time Frame: Baseline to 8 weeks ]
    Test whether RAPA increases aortic compliance in elderly subjects. Aortic MRI will be measured before and after 8 weeks of RAPA using 3T MRI. The study team will quantify distal descending aortic cross-sectional area to assess aortic function/compliance effects.

  4. Aortic Distensibility [ Time Frame: Baseline to 8 weeks ]
    Test whether RAPA increases aortic compliance in elderly subjects. Aortic MRI will be measured before and after 8 weeks of RAPA using 3T MRI. The study team will quantify change in distal descending aortic distensibility to assess aortic function/compliance effects.



Information from the National Library of Medicine

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Ages Eligible for Study:   70 Years to 95 Years   (Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 70-95 years of age.
  • Subjects will be in good general health with all chronic diseases (hypertension, coronary artery disease, etc.) clinically stable. Selected subjects will be in good health (Per the World Health Organization good health will be defined as complete physical, mental, and social well-being and not merely the absence of disease or infirmity.
  • For our purposes all diseases or infirmities will be clinically stable whether managed by medications or not.
  • All ethnicities will be included.
  • For cardiac and brain imaging by MRI, a pre-MRI screening questionnaire will be used to assess MRI safety and neurological health.

Exclusion Criteria:

  • Diabetes, (with A1c ≥6.5 or if treated with medication affecting glucose homeostasis History of skin ulcers or poor wound healing,
  • Smoking,
  • Liver disease,
  • Coumadin anti-coagulation,
  • Treatment with drugs known to affect cytochrome P450 3A (diltiazem, erythromycin, etc) due to its role in RAPA metabolism,
  • Treatment (>30days of therapy or long term) with a systemic immunosuppressant (prednisone, etc.) within the last year,
  • History of recent (within 6 months) Myocardial Infarction or active Coronary Disease,
  • Patients with history of recent (within 6 months) intestinal disorders,
  • Exclusion criteria for MRI scan: known claustrophobia, metal implants in soft tissue of the body including pacemakers, aneurysm clips, ferrous metal fragments not anchored to bone (bullets, BBs, shrapnel, metal shavings), implanted medication pumps, and oral-facial metal appliances that are permanently secured but may result in low image quality. Participants may also be excluded for history of severe head trauma, brain injury, brain surgery, inflammation of the brain, or history of seizures.
  • Female (Studies with mTOR antagonists show that there are often substantial differences in responses by sex, sometimes favoring females, other times males. Our initial pilot study was done in males for this reason and shows trends toward improved cardiac parameters. We will study males in Substudy E, an extension of our prior trial, to generate statistically significant results while obviating potential confounding by differing pharmacodynamics sex effects. Statistically significant results will be used to support larger trials in both sexes.)
  • Positive COVID19 test.

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): NCT04742777


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

Locations
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United States, Texas
Audie L. Murphy Memorial Veterans Hospital Recruiting
San Antonio, Texas, United States, 78229
Contact: Dean L Kellogg, Jr., MD PhD    210-617-5197    kelloggd@uthscsa.edu   
Principal Investigator: Dean L Kellogg, Jr., MD PhD         
The University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Dean Kellogg, Jr., MD         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
The Claude D. Pepper Older Americans Independence Centers
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Dean L Kellogg, Jr., MD PhD The University of Texas Health Science Center at San Antonio
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Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT04742777    
Other Study ID Numbers: HSC20120304H (Addendum)
5P30AG044271-07 ( U.S. NIH Grant/Contract )
First Posted: February 8, 2021    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All IPD that underlie results in a publication will be shared.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Data will become available at study completion at the time of journal publication.

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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.: Yes
Keywords provided by The University of Texas Health Science Center at San Antonio:
geriatrics
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