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

This study is currently recruiting participants.
Verified April 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Mandeep Singh, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01649960
First received: July 23, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Frailty [ Time Frame: Twelve months ] [ Designated as safety issue: No ]
    Frailty will be measured using physical performance tests, gait speed, and grip strength.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age 60 years or older
  2. Patients eligible to undergo cardiac rehabilitation.
  3. Informed written consent.

Exclusion criteria

  1. Class III or IV CHF.
  2. Creatinine > 2.0 mg/dl.
  3. HbA1c > 13%.
  4. Any malignancy
  5. Hematological disorder, including thrombocytopenia, leucopenia.
  6. Noncardiac illness expected to limit survival.
  7. Chronic liver disease.
  8. Suspected or known pregnancy.
  9. Geographically inaccessible or unable to return for follow-up.
  10. Unable to understand or cooperate with protocol requirements.
  11. Post organ transplant or with immune-compromised status
  12. Prior stroke with disability, severe Parkinson disease
  13. Dementia
  14. Post-CABG <3 months or any evidence of active wounds or ulcers.
  15. Anticipating elective surgery in the 3 months following enrollment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01649960

Contacts
Contact: Mandeep Singh, MD, MPH 507-255-3792

Locations
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       singh.mandeep@mayo.edu   
Sub-Investigator: Larry Keenan, MD         
Sub-Investigator: Andrew Moore, MD         
Sub-Investigator: Sandra Birchem, MD         
Sponsors and Collaborators
Mayo Clinic
Investigators
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 7, 2014
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 April 23, 2014