Efficacy Study of Pioglitazone and Glimepiride on the Rate of Progression of Atherosclerotic Disease. (CHICAGO)
|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:||A Double-Blind, Randomized, Comparator-Controlled Study in Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl Versus Glimepiride on the Rate of Progression of Atherosclerotic Disease as Measured by Carotid Intima-Media Thickness|
- Absolute change from Baseline in carotid intima-media thickness. [ Time Frame: Weeks 24, 48 and Final Visit. ] [ Designated as safety issue: No ]
- Change from Baseline in carotid intima-media thickness. [ Time Frame: Weeks 24, 48 and Final Visit. ] [ Designated as safety issue: No ]
- Change from Baseline in coronary artery calcium-volume score. [ Time Frame: At Final Visit ] [ Designated as safety issue: No ]
- Change from Baseline in abdominal adipose tissue content and distribution. [ Time Frame: At Final Visit ] [ Designated as safety issue: No ]
- Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal myocardial infarction and nonfatal stroke [ Time Frame: At each occurrence ] [ Designated as safety issue: No ]
- Incidence of cardiovascular events as a composite of cardiovascular mortality, nonfatal MI, nonfatal stroke, coronary revascularization, carotid endarterectomy/stenting, hospitalization for unstable angina and hospitalization for CHF [ Time Frame: At each occurrence ] [ Designated as safety issue: No ]
|Study Start Date:||October 2003|
|Study Completion Date:||May 2006|
|Primary Completion Date:||May 2006 (Final data collection date for primary outcome measure)|
|Experimental: Pioglitazone QD||
Pioglitazone 15 mg titrated up to 45 mg, tablets, orally, once daily and glimepiride placebo-matching capsules, orally, once daily for up to 72 weeks.
|Active Comparator: Glimepiride QD||
Pioglitazone placebo-matching tablets, orally, once daily and glimepiride 1 mg titrated up to 4 mg, capsules, orally, once daily for up to 72 weeks.
Other Name: Amaryl
Diabetes is a chronic disease with multiple metabolic defects that result in hyperglycemia arising from inadequate insulin activity. Type 2 diabetes usually is the result of a progression from reduced sensitivity of hepatic and peripheral tissue cells to circulating insulin to a progressive inability of the body to produce adequate insulin to overcome insulin resistance, resulting in impaired glucose tolerance and ultimately overt diabetes. In the United States, an estimated 21 million people have diabetes, with type 2 diabetes occurring in approximately 90% to 95% of cases.
Type 2 diabetes also represents an important risk group for the development of accelerated atherosclerosis. Atherosclerosis can be measured with different procedures. One of the noninvasive, commonly used procedures is carotid B-mode ultrasound measurement of carotid intima-media thickness, which has been shown to be a useful measurement for clinical cardiovascular events in multiple studies.
Coronary artery calcification is a marker of coronary artery disease, and electron beam tomography is a sensitive tool for evaluation of coronary artery calcium. Electron beam tomography measurements produce a coronary artery calcium score that represents plaque burden. Subjects with diabetes mellitus have accelerated coronary artery disease. Even after treatment of elevated lipid levels, rates for coronary events still exceed those seen in non-diabetic subjects treated with the same lipid-lowering agents. Diabetic subjects also continue to have increased mortality rates compared with non-diabetic subjects after a myocardial infarction. Therefore, detection of sub-clinical atherosclerosis and prevention of myocardial infarction in subjects with diabetes remains an important priority.
Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd, and depends on the presence of insulin for its mechanism of action. Data suggests that thiazolidinediones may inhibit the development of atherosclerosis in non-diabetic, atherosclerosis mouse models. These findings suggest that this class of drugs may have an effect on vessel walls to suppress development of atherosclerotic lesions.
This study will investigate the effects of pioglitazone and glimepiride on the rate of progression of atherosclerotic disease as measured by carotid intima-media thickness and by electron beam tomography of the coronary arteries in subjects with type 2 diabetes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00225264
|United States, Illinois|
|Chicago, Illinois, United States|
|Study Director:||VP Clinical Science Strategy||Takeda|