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Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
Biosite
Information provided by (Responsible Party):
Darren McGuire, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00424762
First received: January 18, 2007
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: rosiglitazone
Drug: placebo
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 150
Study Start Date: February 2005
Study Completion Date: April 2007
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rosiglitazone
4mg titrated to 8mg daily
Drug: rosiglitazone
6 months of treatment of blinded study drug
Other Name: Avandia
Placebo Comparator: Placebo
blinded matching placebo treatment
Drug: placebo
blinded treatment with matching placebo

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 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.

Comparisons:

  • 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424762

Locations
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9034
Sponsors and Collaborators
University of Texas Southwestern Medical Center
GlaxoSmithKline
Biosite
Investigators
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
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Darren McGuire, Associate Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00424762     History of Changes
Other Study ID Numbers: GSK 102610
Study First Received: January 18, 2007
Results First Received: August 10, 2011
Last Updated: April 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Diabetes Mellitus, Type 2
Congestive Heart Failure
Cardiopulmonary exercise testing
intracellular cardiomyocyte triglycerides
thiazolidinedione
rosiglitazone
nuclear magnetic resonance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Rosiglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014