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

Cardiovascular Diseases Clinical Trial

— PPAR  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00627653
• Other study ID #: AG0093
• Secondary ID: ROI AG15466
• Status: Active, not recruiting
• Phase: N/A
• First received: February 28, 2008
• Last updated: February 18, 2009
• Start date: October 2005
• Est. completion date: December 2009

Study information

• Verified date: February 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• fenofibrate
148mg daily for 30 days

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Coughlin SS, Neaton JD, Sengupta A, Kuller LH. Predictors of mortality from idiopathic dilated cardiomyopathy in 356,222 men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol. 1994 Jan 15;139(2):166-72. — View Citation

Haldeman GA, Croft JB, Giles WH, Rashidee A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J. 1999 Feb;137(2):352-60. — View Citation

Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J. 1991 Mar;121(3 Pt 1):951-7. — View Citation

Ogawa T, Spina RJ, Martin WH 3rd, Kohrt WM, Schechtman KB, Holloszy JO, Ehsani AA. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation. 1992 Aug;86(2):494-503. — View Citation

Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991 Jun;68(6):1560-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Shift in Myocardial substrate utilization in aging hearts		After the day-30 PET scan	No
Secondary	Increased left ventricular function due to shift in substrate use in aging hearts		After the day-30 PET scan	No