Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride

Condition(s) targeted: Diabetes Mellitus, Type 2

Intervention: rosiglitazone (Drug)

Phase: Phase 4

Status: Active, not recruiting

Sponsored by: University of Texas Southwestern Medical Center

Official(s) and/or principal investigator(s):
Darren K McGuire, MD, MHSc, Principal Investigator, Affiliation: University of Texas Southwestern Medical Center
Darren K McGuire, M.D., MHSc, Study Chair, Affiliation: University of Texas Southwestern Medical Center

The purpose of this study is to determine if rosiglitazone treatment improves integrated cardiovascular performance in patients at risk for congestive heart failure. A second aim of this study is to determine if treatment with rosiglitazone decreases intracellular (ectopic) triglyceride (TG) deposition in cardiomyocytes using nuclear magnetic resonance (NMR) techniques, and how changes in intra-myocardial lipid content relate to changes in cardiac structure and function.

Official title: Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Peak VO2 on cardiopulmonary testing at 6 months

Secondary outcome:

New onset peripheral edema

Serum concentrations of b-type natriuretic peptide at baseline and 6 months

Signs and symptoms of congestive heart failure at 1,2,3, and 6 months

Intra-myocardial triglyceride content using in vivo magnetic resonance spectroscopy at 6 months

Detailed description: Cardiovascular disease (CVD), including congestive heart failure (CHF), accounts for over 75% of deaths among patients with diabetes. Thus, it is imperative to rigorously evaluate existing and emerging hypoglycemic therapies with regard to their cardiovascular consequences. The thiazolidinedione (TZD) class of drugs, alone or in combination with other oral hypoglycemic medications or with insulin, has emerged as a safe and effective treatment of hyperglycemia in type 2 diabetes. Both in vitro and in vivo studies have revealed favorable pleiotropic effects of TZD on myocyte and ventricular structure and function. However, approximately 10% of patients taking TZDs develop peripheral edema and some patients have developed heart failure decompensation on the drug. These observations have led to an FDA warning regarding the use of TZDs in patients with or at high risk of developing CHF. The exact effects of TZDs on integrated cardiovascular performance remain unclear. The primary hypothesis of this study is that TZD treatment improves integrated cardiovascular performance in patients at risk for CHF by improving both central (i. e. cardiac output) and peripheral (i. e. vascular resistance) function.

Recently, we have developed a sensitive, reproducible noninvasive assay to measure intra-cardiomyocyte fat, which varies widely in amount between individuals. The relationship between the amount of cardiomyocyte triglyceride accumulation and LV mass and function remains unclear. TZDs have been previously shown to be associated with decreases in the TG content of the liver and muscle. The secondary hypothesis being tested in this study is that TZD treatment improves cardiac function by decreasing intra-cardiac myocyte triglyceride content.

Comparisons:

- Peak VO2 during cardiopulmonary exercise testing in individuals randomized to

rosiglitazone, compared to those on placebo.

- Amount of intra-myocardial triglycerides using NMR techniques in in individuals

randomized to rosiglitazone, compared to those on placebo.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- type 2 diabetes mellitus (prior clinical diagnosis and current use of hypoglycemic

medical therapy or by new diagnosis according to ADA criteria) with at least one of the following:

- prior diagnosis of cardiovascular disease (CAD, MI, revascularization, CVA/TIA,

carotid or peripheral arterial disease)

- at least one additional CVD risk factor (smoking, hypertension,

hypercholesterolemia, albuminuria, family history of premature CAD, or documented hsCRP>3)

Exclusion Criteria:

- treatment with a TZD within prior 6 months

- documented intolerance to TZD

- history or evidence of CHF

- AST/ALT>3X upper limits of normal

- creatinine >2. 5

University of Texas Southwestern Medical Center, Dallas, Texas 75390-9034, United States

Starting date: January 2005
Ending date: April 2007
Last updated: January 23, 2007