Diabetes Mellitus Type 2, Hypercholesterolemia
Conditions
Keywords
atherogenic lipoprotein, cardiovascular disease, coronary artery disease, type 2 diabetes, small, dense LDL
Brief summary
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
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.
Interventions
DRUGezetimibe
ezetimibe 10 mg per day for six weeks
DRUGsimvastatin
Simvastatin 20 mg per day for six weeks
DRUGEzetimibe 10/Simvastatin 20
Ezetimibe 10mg/Simvastatin 20mg per day for six weeks
Sponsors
Essex Pharma GmbH
University Hospital Freiburg
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | baseline and 6 weeks | 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. |
Secondary
| Measure | 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 |
Countries
Germany
Outcome results
None listed