Exercise and Low-Dose Rapamycin in Older Adults With CAD:Cardiac Rehabilitation And Rapamycin in Elderly (CARE) Trial

Summary

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.

Timeline

Start

2012-08

Primary completion

2015-12

Completion

2015-12

Publications

• Results Singh M, Jensen MD, Lerman A, Kushwaha S, Rihal CS, Gersh BJ, Behfar A, Tchkonia T, Thomas RJ, Lennon RJ, Keenan LR, Moore AG, Kirkland JL. Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in Older Adults with Coronary Artery Disease: Results of a Pilot Study. J Frailty Aging. 2016;5(4):204-207. doi: 10.14283/jfa.2016.112.

Drugs

Indications