Clinical trial NCT00953498: Influence of Glitazones on the Vasodilatory Effect of High-density Lipoprotein (HDL) Lipoproteins
Official title: Influence of Glitazones on the Vasodilatory Effect of HDL Lipoproteins and on Phospholipase A2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: diabetes
glitazones
HDL
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2009-08-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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)

Primary outcomes:
measure: Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins
timeFrame: 6 months
Secondary outcomes:
measure: Effect of glitazone therapy on Phospholipase A2 level
timeFrame: 6 months
measure: Analyze the glycemic response to glitazones according to baseline clinical and biological characteristics
timeFrame: 6 months
measure: Look for possible differences between pioglitazone and rosiglitazone for their effects on HDL lipoproteins and phospholipase A2
timeFrame: 6 months
Other outcomes:
Locations:
city: Dijon
country: France
facility: Service Endocrinologie-diabétologie, Hôpital du Bocage CHU
Study officials:
affiliation: CHU Dijon
name: Bruno L Vergès, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Persegol L, Verges 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. doi: 10.1007/s00125-006-0244-1. Epub 2006 Apr 5.
citation: Verges B, Radu L, Baillot-Rudoni S, Brindisi MC, Poussier A, Bouillet B, Petit JM, Duvillard L. Low HDL-cholesterol: a strong predictor of glycemic response to glitazone treatment in patients with type 2 diabetes. Diabetes Res Clin Pract. 2011 Jul;93(1):e44-8. doi: 10.1016/j.diabres.2011.04.005. Epub 2011 May 6.