Anti-Inflammatory Effects of Pioglitazone

Study Overview
=================
Brief Summary
-----------------
There is increasing evidence that inflammation plays a role in progression and destabilization of atherosclerotic plaque. FDG-PET can visualize activated metabolic activity of inflammatory cells. It is possible that FDG-PET can detect atherosclerotic plaque inflammation and that FDG-PET can monitor the effect of pioglitazone on plaque inflammation.

Detailed Description
-----------------
Atherosclerotic patients with impaired glucose tolerance and type 2 diabetes will undergo the FDG-PET/CT imaging at baseline and again following 4 months after treatment. Patients who meet eligibility criteria will be titrated up to a maximum of 30 mg/day pioglitazone or 4 mg/day glimepiride. Physical examinations will be done at baseline, 4 months, and 12 months. During study, subjects will have body weight, and vital signs (HR, BP, etc) assessed as well as waist circumference. Laboratory assessments will be done at each baseline, 4 month.

Official Title
-----------------
Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT

Conditions
-----------------
Impaired Glucose Tolerance, Type 2 Diabetes Mellitus, Atherosclerosis

Intervention / Treatment
-----------------
* Drug: Pioglitazone
* Drug: Glimepiride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects between the ages of 35 and 85 years Subjects with impaired glucose tolerance and type 2 diabetes, who had atherosclerosis detected by carotid ultrasound and/or CT Subjects who had vascular FDG uptake by FDG-PET Exclusion Criteria: Subjects with insulin treatment Subjects with uncontrolled diabetes, hypertension, symptomatic coronary artery disease, symptomatic cerebrovascular disease Subjects taking more than three antidiabetic medications Subjects taking anti-platelet, statins, antidiabetic agents, thiazolidinediones (TZDs) within 8 weeks prior to randomization Subjects with cardiac failure (New York Heart Association Class > III) or left ventricular dysfunction (LVEF < 40%) Subjects with systemic disorders such as active inflammatory, liver, renal, hematopoietic, and malignant disease

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>up to 30 mg pioglitazone, tablet, orally, once daily | Drug: Pioglitazone<br>* Subjects who meet eligibility criteria will be titrated up to a maximum of 30 mg/day pioglitazone.<br>* Other names: CAS number: 111025-46-8, ATC code: A10BG03;|
| Active Comparator: 2<br>up to 4 mg/day glimepiride, tablet, orally, once daily | Drug: Glimepiride<br>* Subjects who meet eligibility criteria will be titrated up to a maximum of 4 mg/day glimepiride.<br>* Other names: CAS number: 93479-97-1, ATC code: A10BB12;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of treatment on the nominal change in FDG uptake of atherosclerotic plaque from baseline after 4 months of treatment as measured by FDG-PET/CT imaging. |  | Baseline and 4 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in plasma glucose/insulin homeostatic parameters and circulating markers of atherosclerosis |  | Baseline and 4 months and 5 years after treatment | 
| Change from baseline in visceral fat |  | Baseline and 4 months and 5 years after treatment | 
| All cardiovascular events and all cause death for 5 years |  | Baseline and 4 months and 5 years after treatment |