Influence of Glitazones on the Vasodilatory Effect of High-density Lipoprotein (HDL) Lipoproteins

Study Overview
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Brief Summary
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HDL from patients with type 2 diabetes show a significant reduction of their endothelium-dependent vasodilatory effect. The primary objective of the study is to analyze whether treatment with glitazones (pioglitazone and rosiglitazone)may improve the endothelium-dependent vasodilatory effect of HDL lipoproteins in patients with type 2 diabetes. The secondary objectives are: to analyze the effect of glitazone treatment on phospholipase A2 to look for possible differences between the effects of pioglitazone and those of rosiglitazone to analyze the glycemic response to glitazone therapy according to clinical and biological baseline characteristics.

Detailed Description
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The study will be performed as follows: At baseline, before initiating glitazone treatment, clinical data will be recorded and blood samples will be obtained for biological measurements (blood glucose, HbA1c, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, liver enzymes), phospholipase A2 measurement and the study of the vasodilatory effect of HDL particles.For this purpose, we will study,using rabbit aorta rings,the ability of HDL to suppress the inhibition of vasodilation that is induced by oxidised LDL. For all the patients included into the study, a treatment by pioglitazone (at an initial dose of 30 mg/day) or rosiglitazone (at an initial dose of 4 mg/day) will be given by randomization. A visit will be performed at week 12, in order to titrate the glitazone dose (up to 45 mg/day for pioglitazone, up to 8 mg/day for rosiglitazone)according to HbA1c level and values of self-monitoring blood glucose. At week 24, the last visit will take place. During this visit, clinical data will be recorded and blood samples will be obtained for biological measurements (blood glucose, HbA1c, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, liver enzymes), phospholipase A2 measurement and the study of the vasodilatory effect of HDL particles.

Official Title
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Influence of Glitazones on the Vasodilatory Effect of HDL Lipoproteins and on Phospholipase A2

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: pioglitazone
* Drug: rosiglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with type 2 diabetes treated by oral antidiabetic agents (except glitazones) and/or insulin age> 18 years HbA1c > 6.5% Exclusion Criteria: renal failure heart failure primary hyperlipidemia pregnancy treatment that may modify lipid metabolism (glucocorticoids, oestrogens, retinoids, HIV antiviral drugs)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pioglitazone<br>treatment with pioglitazone (dose from 30 mg:day to 45 mg/day) | Drug: pioglitazone<br>* After randomization, patients will be treated by pioglitazone or rosiglitazone<br>* Other names: rosiglitazone: AVANDIA;|
| Active Comparator: rosiglitazone<br>treatment with rosiglitazone at a dose between 4mg and 8 mg/day | Drug: rosiglitazone<br>* treatment with rosiglitazone at a dose between 4mg and 8 mg/day<br>* Other names: rosiglitazone: AVANDIA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of glitazone therapy on Phospholipase A2 level |  | 6 months | 
| Analyze the glycemic response to glitazones according to baseline clinical and biological characteristics |  | 6 months | 
| Look for possible differences between pioglitazone and rosiglitazone for their effects on HDL lipoproteins and phospholipase A2 |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, glitazones, HDL