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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00627653
Recruitment Status : Unknown
Verified February 2009 by National Institute on Aging (NIA).
Recruitment status was:  Active, not recruiting
First Posted : March 3, 2008
Last Update Posted : February 19, 2009
Information provided by:
National Institute on Aging (NIA)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Drug: fenofibrate Not Applicable

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: PET (Positron Emission Tomography) Detection of the Effects of Aging on the Human Heart (Aim #2 Effect of a PPAR-Alpha Agonist on the Age Related Changes in Myocardial Metabolism and Mechanical Function)
Study Start Date : October 2005
Estimated Primary Completion Date : December 2009
Estimated Study Completion Date : December 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Fenofibrate
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 1 Drug: fenofibrate
148mg daily for 30 days
Other Name: Lofibra; TriCor

Primary Outcome Measures :
  1. Shift in Myocardial substrate utilization in aging hearts [ Time Frame: After the day-30 PET scan ]

Secondary Outcome Measures :
  1. Increased left ventricular function due to shift in substrate use in aging hearts [ Time Frame: After the day-30 PET scan ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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:

  • Coronary artery disease
  • High blood pressure
  • Current smoker
  • Diabetes mellitus
  • Cardiovascular disease (signs and symptoms of any kind)
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00627653

United States, Missouri
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Sponsors and Collaborators
National Institute on Aging (NIA)
Principal Investigator: Robert Gropler, MD Washington University School of Medicine