Effect of Ezetimibe or Simvastatin or Both on Low Densitiy Lipoprotein -Subfractions in Patients With Type 2 Diabetes

University Hospital Freiburg41 enrolled

Overview

It is of interest how ezetimibe alone or in combination with statin may influence atherogenic dense Low Density Lipoprotein (dLDL) in patients with type 2 diabetes mellitus. The primary objective of this study will be whether there is a change of the concentrations of Apolipoprotein B (ApoB) in dLDL from baseline in each of the 3 treatment groups.

The selective cholesterol resorption inhibitor ezetimibe belongs to a new class of cholesterol lowering drugs. It is of interest how ezetimibe alone or in combination with statin may influence atherogenic dense Low Density Lipoprotein (dLDL) in patients with type 2 diabetes mellitus. The primary objective of this study will be whether there is a change of the concentrations of Apolipoprotein B (ApoB) in dLDL from baseline in each of the 3 treatment groups. The comparison between treatment groups is exploratory due to insufficient power to detect any change between treatments.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus Type 2 Hypercholesterolemia

Interventions

ezetimibeDRUG

ezetimibe 10 mg per day for six weeks

simvastatinDRUG

Simvastatin 20 mg per day for six weeks

Ezetimibe 10/Simvastatin 20DRUG

Ezetimibe 10mg/Simvastatin 20mg per day for six weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * men \> 18 and ≤ 75 years * post-menopausal women ≤ 75 years (follicle stimulating hormone (FSH) \>30 mIU/ml, women \> 60 years FSH \> 20 mIU/ml ) * well controlled diabetes mellitus type II (glycohaemoglobin ≤ 8,0 %) * LDL-cholesterol ≤ 160 mg/dl * LDL-subfractions: concentration of apoB-100 in dLDL (LDL-5 und LDL-6) \> 25 mg/dl * written informed consent Exclusion Criteria: * participation in a clinical trial within the last 30 d before screening- visit * patient is unable to give written informed consent * Body mass index \<15 kg/m² and \> 35 kg/m² * clinical atherosclerotic disease (coronary heart disease, peripheral artery disease, carotid artery disease) * malignoma * uncontrolled arterial hypertension (\>160/\>100 mmHg) * clinically relevant disease of liver and/or kidneys * clinically relevant endocrinally or hematologic problems * allergy to study medication (Ezetimibe and/or Simvastatin) * alcohol- or drug abuse * laboratory: alanine aminotransferase, aspartate aminotransferase, total bilirubin \> 3 x ULN, creatine kinase \> 5 x ULN * Concurrent treatment with potent CYP3A4-inhibitors (e.g. itraconazole, ketoconazole, HIV-protease-inhibitors, erythromycin, clarithromycin, telithromycin und nefazodone) * other relevant diseases

Locations (2)

Institut für Stoffwechselforschung

Frankfurt, Germany, Germany

Stephan Jacob, MD

Villingen-Schwenningen, Germany, Germany

Outcomes

Primary Outcomes

Change of the concentration of apolipoprotein B (ApoB) in dense Low Densitiy Lipoprotein (dLDL) from baseline with ezetimibe, simvastatin or the combination of both drugs

multicentre, randomized, open-label study investigation in 6-week effect of ezetimibe (10mg/d), simvastatin (20mg/d) or combination of ezetimibe 10mg/simvastatin 20mg/d on concentrations of dLDL separated by preparative gradient ultracentrifugation in patients with type 2 diabetes.