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

Phase 4

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: pioglitazone; Drug: rosiglitazone

• Registration Number: NCT00953498
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

Brief Summary

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

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.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2009-08-05
• Study First Submitted QC: 2009-08-05
• Study First Posted: 2009-08-06
• Primary Completion: 2012-03
• Study Completion: 2012-03
• Status Verified: 2013-08
• Last Update Submitted: 2013-08-30
• Last Update Posted: 2013-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
pioglitazone	pioglitazone	treatment with pioglitazone (dose from 30 mg:day to 45 mg/day)
rosiglitazone	rosiglitazone	treatment with rosiglitazone at a dose between 4mg and 8 mg/day

Primary Outcome Measures

Name	Time	Method
Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins	6 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Service Endocrinologie-diabétologie, Hôpital du Bocage CHU; 🇫🇷 Dijon, France