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

NCT01649960 | Completed Phase 1 DMC

• 1 other identifier: 11-007896
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Aging; CAD

Keywords

Aging; Biomarkers; CAD

Outcome Measures

Primary Outcomes (1)

• Frailty

  Frailty will be measured using physical performance tests, gait speed, and grip strength.

  Twelve months

Secondary Outcomes (1)

• Senescent-associated secretory phenotype

  twelve months

Other Outcomes (2)

• Quality of life

  Twelve months

• Mitochondrial DNA copy number and quantitation of senescent preadipocytes

  12 weeks, before and after cardiac rehabilitation

Study Arms (1)

Rapamycin

OTHER

Oral rapamycin was given during the nonrandomized phase of the study. The doses that were used of rapamycin were 0.5mg, 1mg, or 2mg.

Drug: Rapamycin

Interventions

Rapamycin DRUG

Oral tablets were given in the dose of 0.5mg, 1mg, or 2mg once a day. This was a pilot study and the serum rapamycin levels were kept below 6ng/ml.

Rapamycin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 years or older
• Patients eligible to undergo cardiac rehabilitation.
• Informed written consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester and Mayo Health System sites in Austin and Albert Lea, Minnesota

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 27883166 RESULT

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Mandeep Singh, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 25, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 7, 2016

Record last verified: 2016-12

Locations

US (1)