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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00953498
• Other study ID #: AFSSAPS A70516-50
• Status: Completed
• Phase: Phase 4
• First received: August 5, 2009
• Last updated: August 30, 2013
• Start date: October 2007
• Est. completion date: March 2012

Study information

• Verified date: August 2013
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Type 2 Diabetes

Intervention

Drug:
• pioglitazone
After randomization, patients will be treated by pioglitazone or rosiglitazone
• rosiglitazone
treatment with rosiglitazone at a dose between 4mg and 8 mg/day

Locations

Country	Name	City	State
France	Service Endocrinologie-diabétologie, Hôpital du Bocage CHU	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Action of glitazone on the endothelium-dependent vasodilatory effects of HDL lipoproteins		6 months	No
Secondary	Effect of glitazone therapy on Phospholipase A2 level		6 months	No
Secondary	Analyze the glycemic response to glitazones according to baseline clinical and biological characteristics		6 months	No
Secondary	Look for possible differences between pioglitazone and rosiglitazone for their effects on HDL lipoproteins and phospholipase A2		6 months	No