Exercise and Low-Dose Rapamycin in Older Adults With CAD:Cardiac Rehabilitation And Rapamycin in Elderly (CARE) Trial
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Purpose
The investigators will do the study in two phases. The first phase will be a pilot study on up to 18 participants [patients 70 years or older with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) who 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 70 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Aging CAD |
Drug: Rapamycin |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| 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.
| Estimated Enrollment: | 78 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | January 2015 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Rapamycin versus placebo
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.
|
Drug: Rapamycin
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.
Other Name: Rapamycin
|
| Placebo Comparator: Rapamycin |
Show Detailed Description Eligibility| Ages Eligible for Study: | 70 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Age 70 years or older
- Post-revascularization patients being enrolled in CR.
- Informed written consent.
Exclusion criteria
- Class III or IV CHF.
- Creatinine > 2.0 mg/dl.
- HbA1c > 13%.
- Any malignancy
- Hematological disorder, including thrombocytopenia, leucopenia.
- Noncardiac illness expected to limit survival.
- Chronic liver disease.
- Suspected or known pregnancy.
- Geographically inaccessible or unable to return for follow-up.
- Unable to understand or cooperate with protocol requirements.
- Post organ transplant or with immune-compromised status
- Prior stroke with disability, severe Parkinson disease
- Dementia
- Post-CABG <3 months or any evidence of active wounds or ulcers.
- Anticipating elective surgery in the 3 months following enrollment.
Contacts and Locations| United States, Minnesota | |
| Mayo Clinic in Rochester | Recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Mandeep Singh, MD singh.mandeep@mayo.edu | |
| Principal Investigator: | Mandeep Singh, MD | Mayo Clinic |
More Information
No publications provided
| Responsible Party: | Mandeep Singh, Principal Investigator, Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT01649960 History of Changes |
| Other Study ID Numbers: | 11-007896 |
| Study First Received: | July 23, 2012 |
| Last Updated: | April 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Mayo Clinic:
|
Aging Biomarkers CAD |
Additional relevant MeSH terms:
|
Coronary Artery Disease Coronary Disease Myocardial Ischemia Heart Diseases Cardiovascular Diseases Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases Sirolimus Everolimus |
Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antifungal Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on June 18, 2013