Effect of Rosiglitazone Versus Placebo on Cardiovascular Performance and Myocardial Triglyceride

April 2, 2012 updated by: Darren McGuire, 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: rosiglitazone
4mg titrated to 8mg daily
Drug: rosiglitazone
6 months of treatment of blinded study drug
Other Names:
  • Avandia
Placebo Comparator: Placebo
blinded matching placebo treatment
Drug: placebo
blinded treatment with matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Oxygen Uptake (VO2)
Time Frame: 6 months
measurement of peak oxygen uptake (VO2peak) during treadmill exercise, in units of milliliters of oxygen per kilogram of fat-free mass per minute
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intra-myocardial Triglyceride Content Using in Vivo Magnetic Resonance Spectroscopy at 6 Months
Time Frame: 6 months
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 (%)
6 months
Percentage of Patients Developing New or Worsening Peripheral Edema
Time Frame: 6 months
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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

April 1, 2007

Study Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

January 18, 2007

First Submitted That Met QC Criteria

January 18, 2007

First Posted (Estimate)

January 22, 2007

Study Record Updates

Last Update Posted (Estimate)

April 4, 2012

Last Update Submitted That Met QC Criteria

April 2, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GSK 102610

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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