Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride|
- Peak Oxygen Uptake (VO2) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]measurement of peak oxygen uptake (VO2peak) during treadmill exercise, in units of milliliters of oxygen per kilogram of fat-free mass per minute
- Intra-myocardial Triglyceride Content Using in Vivo Magnetic Resonance Spectroscopy at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]proton magnetic resonance spectroscopy determination of intra-myocardial triglyceride content at baseline and after 6 months, with triglyceride quantified analyzing fat and water signals assuming monoexponential signal decay and expressed as a percentage of fat-to-water (%)
- Percentage of Patients Developing New or Worsening Peripheral Edema [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]clinical evaluation of peripheral edema by physical exam at each study visit by a cardiologist using standard clinical severity scale 0-4, with new/worsening edema defined as any edema in patients with none at baseline, OR increase in severity by 2 or more points in patients with edema at baseline
|Study Start Date:||February 2005|
|Study Completion Date:||April 2007|
|Primary Completion Date:||April 2007 (Final data collection date for primary outcome measure)|
4mg titrated to 8mg daily
6 months of treatment of blinded study drug
Other Name: Avandia
Placebo Comparator: Placebo
blinded matching placebo treatment
blinded treatment with matching placebo
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 a Food and Drug Administration (FDA) warning regarding the use of TZDs in patients with or at high risk of developing congestive heart failure (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.
- Peak oxygen uptake (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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00424762
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390-9034|
|Principal Investigator:||Darren K McGuire, MD, MHSc||University of Texas Southwestern Medical Center|
|Study Chair:||Darren K McGuire, M.D., MHSc||University of Texas Southwestern Medical Center|