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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effect of Ezetimibe 10 mg, Simvastatin 20 mg and the Combination of Simvastatin 20 mg Plus 10 mg Ezetimibe on Low Density Lipoprotein (LDL)-Subfractions in Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus Type 2, Hypercholesterolemia

Intervention / Treatment
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* Drug: ezetimibe
* Drug: simvastatin
* Drug: Ezetimibe 10/Simvastatin 20


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ezetimibe 10mg/d<br>intake of ezetimibe 10mg per day for six weeks after wash-out | Drug: ezetimibe<br>* ezetimibe 10 mg per day for six weeks<br>* Other names: Ezetrol 10 mg;|
| Active Comparator: Simvastatin 20 mg per day<br>intake of simvastatin 20 mg per day for six weeks after wash-out | Drug: simvastatin<br>* Simvastatin 20 mg per day for six weeks<br>* Other names: Zocor MSD;|
| Active Comparator: Ezetimibe 10 mg/d and Simvastatin 20mg/d<br>intake of ezetimibe 10 mg and simvastatin 20 mg per day for six weeks after wash-out | Drug: Ezetimibe 10/Simvastatin 20<br>* Ezetimibe 10mg/Simvastatin 20mg per day for six weeks<br>* Other names: Inegy 10/20;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the concentrations of Total Cholesterol |  | baseline and 6 weeks | 
| Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol |  | baseline and 6 weeks | 
| Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol |  | baseline and 6 weeks | 
| Change of the concentrations of triglycerides |  | baseline and 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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atherogenic lipoprotein, cardiovascular disease, coronary artery disease, type 2 diabetes, small, dense LDL