Clinical trial NCT04742777: Effect of mTOR Inhibition & Other Metabolism Modulating Interventions on the Elderly [SubStudy Rapa & cMRI to Evaluate Cardiac Function]
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Aging
Keywords: geriatrics
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: The Claude D. Pepper Older Americans Independence Centers
name: National Institute on Aging (NIA)
First posted: 2021-02-08
Enrollment: 12
Sex: ALL
Minimum age (years): 70
Maximum age (years): 95
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Rapamycin 1mg for 8 weeks
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: Inclusion Criteria:

* men and women 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,
* 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.
* Positive COVID19 test.

Primary outcomes:
measure: Systolic Function
timeFrame: Baseline to 8 weeks
measure: Diastolic Function
timeFrame: Baseline to 8 weeks
measure: Aortic Cross-Sectional Area
timeFrame: Baseline to 8 weeks
measure: Aortic Distensibility
timeFrame: Baseline to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Audie L. Murphy Memorial Veterans Hospital
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center at San Antonio
name: Dean L Kellogg, Jr., MD PhD
role: PRINCIPAL_INVESTIGATOR
References: