Treatment of Coronary Atherosclerosis by Insulin Sensitizers in Insulin-Resistant Patients
|ClinicalTrials.gov Identifier: NCT00155350|
Recruitment Status : Unknown
Verified August 2005 by National Taiwan University Hospital.
Recruitment status was: Recruiting
First Posted : September 12, 2005
Last Update Posted : February 27, 2006
|Condition or disease||Intervention/treatment||Phase|
|Coronary Atherosclerosis Inflammation Coronary Heart Disease||Drug: pioglitazone||Phase 4|
Background: Type 2 diabetes and its antecedent, metabolic syndrome, are important risk factors for premature and accelerated atherosclerotic cardiovascular diseases. However, glycemic control by provision of endogenous or exogenous insulin induced only modest and not statistically significant reduction of the risk of myocardial infarction. We and other investigators have demonstrated that the use of insulin sensitizer, thiazolidinediones, resulted in favorable antiatherosclerotic effects in patients with type 2 diabetes or non-diabetic metabolic syndrome. It has become increasingly clear that morbidity and mortality associated with coronary artery disease (CAD) are often associated with lesions that are not obstructive but prone to rupture, the so-called vulnerable plaques. Conventional coronary angiography is not suitable for identifying vulnerable plaques. They may be detected by intravascular ultrasound (IVUS) and recently developed high-resolution 16-slice multi-detector computed tomography (MDCT). Nevertheless, whether this modality could be used as a guide for optimizing medical treatment of CAD has never been explored in the medical literature. In this study, we will evaluate the efficacy of pharmacological therapy targeted to reduce insulin resistance on the progression and compositional change of non-obstructive coronary atherosclerotic plaques and coronary calcification by serial IVUS/MDCT follow-up in patients with type 2 diabetes or non-diabetic metabolic syndrome during a 2-year period.
Methods and Expected Results: Patients aged ≥18 years conformed to the diagnosis of type 2 diabetes or metabolic syndrome criteria in ATP III and with objective evidence of myocardial ischemia will undergo EBCT, MDCT coronary angiography, percutaneous coronary angiography and intervention if appropriate, and IVUS study if non-obstructive coronary plaques are identified in the MDCT examination. Patients deemed eligible (with one or more ≥ 20% and < 70% stenosis in at least one coronary artery) will then be randomly assigned in a 1:1 ratio to receive pioglitazone (30 mg/d) or placebo in an open-label fashion. Patients with type 2 diabetes assigned to the placebo group are not allowed to be treated with any insulin sensitizer. The target for glycemic control in patients with type 2 diabetes in both groups is reduction of HbA1c to ≤ 7.0%. A total of 120 patients are planned to be included, and the follow-up period is 2 years. To assess the progression of coronary atherosclerosis, MDCT coronary angiography/scanning will be performed at baseline and 3, 6, 12, and 24 months of follow-up. Follow-up coronary angiography and intravascular ultrasound study will be performed at 6 months if patients agree. Blood samples will also be obtained at baseline and 3, 6, 12, and 24 months of follow-up for the measurement of various conventional and novel coronary risk factors. We also obtain DNA specimen from blood drawn at baseline for genotyping. The primary end-points include changes from baseline in total plaque volume, plaque characteristics (as determined by CT-density values and other morphological features), and total coronary calcium score. The secondary end-points include percent change from baseline in calcium volume score in each coronary artery, percent change from baseline in plasma glucose/insulin homeostatic parameters and various risk markers, and the occurrence of a composite of major cardiovascular events (death from any cause, non-fatal myocardial infarction, stroke, and target vessel revascularization).
Clinical Significance: This is the first human study to assess the antiatherosclerotic effects of insulin sensitizer by directly visualizing the atherosclerotic plaques of the whole coronary trees. It will provide us great insights regarding the evolution of coronary plaques and techniques of measuring the total vulnerability burden of the coronary arteries.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Treatment of Coronary Atherosclerosis and Calcification by Insulin Sensitizers in Insulin-Resistant Patients: Evaluated by EBCT, 16-Slice MDCT Coronary Angiography/Scanning, and Intravascular Ultrasound|
|Study Start Date :||November 2004|
|Estimated Study Completion Date :||December 2007|
- changes from baseline in total plaque volume, plaque characteristics (as determined by computed tomography [CT]-density values and other morphological features), and total coronary calcium score
- percent change from baseline in calcium volume score in each coronary artery
- percent change from baseline in plasma glucose/insulin homeostatic parameters and various risk markers
- and the occurrence of a composite of major cardiovascular events
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00155350
|Contact: Tzung-Dau Wang, MD, PhD||886-2-2312-3456 ext firstname.lastname@example.org|
|Division of Cardiology, Department of Internal Medicine and Department of Medical Imaging, National Taiwan University Hospital||Recruiting|
|Taipei, Taiwan, 100|
|Contact: Tzung-Dau Wang, MD, PhD 886-2-2312-3456 ext 5632 email@example.com|
|Principal Investigator: Tzung-Dau Wang, MD, PhD|
|Sub-Investigator: Wen-Jeng Lee, MD|
|Principal Investigator:||Tzung-Dau Wang, MD, PhD||National Taiwan University Hospital|