title: The effect of rosiglitazone on integrated cardiovascular performance, cardiac structure, function and myocardial triglyceride: trial design and rationale.
abstract: The thiazolidinedione (TZD) class of medications has been associated with increased risk for peripheral oedema, as well as incident and worsening heart failure (HF). The mechanism of these observed effects remains unclear. Here we present the rationale and study design for a randomised clinical trial designed to evaluate the cardiac effects of rosiglitazone on integrated cardiovascular performance, cardiac structure and function. The study is a randomised, single-centre, double-blind, placebo-controlled, parallel-group clinical trial to evaluate the effect of rosiglitazone on integrated cardiovascular performance in a cohort of patients with type 2 diabetes mellitus (T2DM) at increased risk for developing heart failure (HF). Participants will be randomised to receive rosiglitazone or matching placebo for six months. All subjects will undergo maximal treadmill cardiopulmonary exercise testing at baseline and after six months on study drug, with the primary trial end point of peak oxygen uptake indexed to fat-free mass (VO 2peak-FFM). Approximately two-thirds of the study cohort will undergo cardiac magnetic resonance imaging (MRI) and spectroscopy (MRS) at baseline and after six months of study therapy to assess cardiac structure, function and myocardial triglyceride content. While concerns for peripheral oedema and HF continue to confound clinical use of TZD medications, the direct cardiac effects of these drugs remain poorly understood and the clinical relevance of these clinical observations remains unclear. The present study will combine a series of state-of-the-art assessments to evaluate the cardiac effects of rosiglitazone treatment.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9047, USA. Darren.McGuire@UTSouthwestern.edu
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Raphael
authors.initials: R
authors.lastname: See
authors.forename: Shuaib M
authors.initials: SM
authors.lastname: Abdullah
authors.forename: Peter G
authors.initials: PG
authors.lastname: Snell
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: McGavock
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Lidia S
authors.initials: LS
authors.lastname: Szczepaniak
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000503:physiopathology; D005080:Exercise Test; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D005343:Fibrinolytic Agents; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone