Exercise and Low-Dose Rapamycin in Older Adults With CAD:Cardiac Rehabilitation And Rapamycin in Elderly (CARE) Trial
The investigators will do the study in two phases. The first phase will be a pilot study on up to 18 participants [patients 60 years or older with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) or patients who are eligible to undergo and participate in cardiac rehabilitation (CR)]; up to 6 participants each will be given oral daily rapamycin (0.5, 1, and 2mg) dose for the duration of CR. Baseline and follow-up data will be collected for age-associated impairment (AAI): frailty (primary endpoint) and quality of life (QOL),senescent-associated secretory phenotype (SASP)and abdominal/thigh subcutaneous adipose biopsy for measurement of adipocyte mitochondrial DNA copy number and to quantitate the number of senescent preadipocytes. Safety of rapamycin will be assessed by periodic clinical follow-up, blood draws, and serum rapamycin levels. Following completion of the pilot phase, the data will be analyzed. If favorable changes are noted in the SASP or AAI, the investigators will start a phase 2 randomized trial.
Second phase: In a prospective, randomized, clinical trial design, patients 60 years or older will be randomized at the time of CR to a standardized exercise protocol, or exercise protocol with the addition of low-dose rapamycin to test the hypothesis whether low-dose rapamycin (demonstrated in the pilot trial to improve SASP/AAI) will improve measures of AAI, SASP, or findings on the fat biopsy as compared to exercise alone. The null hypotheses are that there is no improvement with rapamycin in measures of AAI or SASP.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Role of Exercise and Low-Dose Rapamycin on Age-Associated Impairments in Older Adults With Coronary Artery Disease: Cardiac Rehabilitation And Rapamycin in Elderly (CARE) Trial|
- Frailty [ Time Frame: Twelve months ] [ Designated as safety issue: No ]Frailty will be measured using physical performance tests, gait speed, and grip strength.
- Senescent-associated secretory phenotype [ Time Frame: twelve months ] [ Designated as safety issue: No ]The SASP will include interleukin 6, Matrix metalloproteinase 3, and Monocyte chemotactic protein 1.
- Quality of life [ Time Frame: Twelve months ] [ Designated as safety issue: No ]Short-form 12 will be measured
- Mitochondrial DNA copy number and quantitation of senescent preadipocytes [ Time Frame: 12 weeks, before and after cardiac rehabilitation ] [ Designated as safety issue: No ]These variables will be analyzed by a fat biopsy (abdominal/thigh) before and following completion of cardiac rehabilitation.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Rapamycin
Oral rapamycin or placebo will be given during the randomized phase of the study. The doses that will be used of rapamycin could be 0.5mg, 1mg, or 2mg depending upon the results of the pilot phase and its effect on biomarkers and physical performance.
Oral tablets will be given in the dose of 0.5mg, 1mg, or 2mg once a day. The dose used in the randomized trial will be determined from the pilot trial. We will keep the serum rapamycin levels below 6ng/ml.
|Placebo Comparator: Placebo|
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01649960
|Contact: Mandeep Singh, MD, MPH||507-255-3792|
|United States, Minnesota|
|Mayo Clinic in Rochester and Mayo Health System sites in Austin and Albert Lea, Minnesota||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Mandeep Singh, MD email@example.com|
|Sub-Investigator: Larry Keenan, MD|
|Sub-Investigator: Andrew Moore, MD|
|Sub-Investigator: Sandra Birchem, MD|
|Principal Investigator:||Mandeep Singh, MD||Mayo Clinic|