Effect of a PPAR-Alpha Agonist on the Age Related Changes in Myocardial Metabolism and Mechanical Function

National Institutes of Health (NIH)

Status

Unknown

Conditions

Cardiovascular Diseases

Treatments

Drug: fenofibrate

Study type

Interventional

Funder types

NIH

Identifiers

NCT00627653

AG0093

ROI AG15466

Details and patient eligibility

About

The purpose of this study is to determine if treatment with a drug called fenofibrate, which is a PPAR-alpha agonist and controls how the heart metabolizes fats, will reverse the age-related decline in cardiac fat metabolism and mechanical function.

Full description

In older Americans, cardiovascular disease is the leading cause of death and disability. It has been shown recently that with aging the human heart exhibits a decline in myocardial fatty acid utilization (MFAU) and oxidation (MFAO) and that these metabolic changes are paralleled by a decline in mechanical function. It has also been shown that peroxisome proliferator activated receptor alpha (PPAR-alpha) activates the expression of the genes encoding enzymes involved in mitochondrial fatty acid transport and oxidation. There is both indirect and direct evidence that PPAR-alpha-mediated responses decrease with age. Consequently, we hypothesize that changes in fatty acid in the aging heart may be mediated, at least in part, via a decline in PPAR-alpha-mediated responses. Thus, administration of a PPAR-alpha agonist to older humans will result in a shift in cardiac fatty acid metabolism to that more closely seen in younger humans and this shift will be paralleled by an improvement in cardiac mechanical function.

To prove or disprove this hypothesis, we will determine, in aged and young healthy volunteers, whether stimulation of PPAR-alpha using the partial agonist, fenofibrate, shifts myocardial substrate utilization by increasing MFAU and MFAO, and whether these changes are associated with an increase in left ventricular function. Study participants will have 4 clinic visits, each lasting approximately 5 hours.

Enrollment

60 estimated patients

Sex

All

Ages

21 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Aged 60-75 or 21-35
Normal glucose tolerance test
Normal plasma fasting lipid panel (fasting total cholesterol less than 220 mg/dL)
Normal rest/stress echocardiogram
BMI (body mass index) less than 30 kg/m2
Must be sedentary (active, but do not engage in regular exercise or jobs that require strenuous exertion)

Exclusion criteria