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

Condition(s) targeted: Type 2 Diabetes

Intervention: pioglitazone (Drug); rosiglitazone (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Centre Hospitalier Universitaire Dijon

Official(s) and/or principal investigator(s):
Bruno L Vergès, MD,PhD, Principal Investigator, Affiliation: CHU Dijon

Overall contact:
Bruno L Vergès, MD, PhD, Phone: 33 3 80 29 34 53, Email: bruno.verges@chu-dijon.fr

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.

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

Study design: Treatment, Randomized, Open Label, Uncontrolled, Parallel Assignment, Efficacy Study

Primary outcome: Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins

Secondary outcome:

Effect of glitazone therapy on Phospholipase A2 level

Analyze the glycemic response to glitazones according to baseline clinical and biological characteristics

Look for possible differences between pioglitazone and rosiglitazone for their effects on HDL lipoproteins and phospholipase A2

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

Bruno L Vergès, MD, PhD, Phone: 33 3 80 29 34 53, Email: bruno.verges@chu-dijon.fr

Service Endocrinologie-diabétologie, Hôpital du Bocage CHU, Dijon 21000, France; Recruiting
Bruno L Vergès, MD,PhD, Phone: 33 3 80 29 34 53, Email: bruno.verges@chu-dijon.fr
Isabelle Robin, PhD, Phone: 33 3 80 29 34 53, Email: isabelle.robin@chu-dijon.fr
Bruno L Vergès, MD,PhD, Principal Investigator

Related publications:

Perségol L, Vergès B, Foissac M, Gambert P, Duvillard L. Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation. Diabetologia. 2006 Jun;49(6):1380-6. Epub 2006 Apr 5.

Starting date: October 2007
Ending date: March 2010
Last updated: September 2, 2009