Clinical trial NCT01384058: Effect of Ezetimibe or Simvastatin or Both on Low Densitiy Lipoprotein -Subfractions in Patients With Type 2 Diabetes
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus Type 2
Hypercholesterolemia
Keywords: atherogenic lipoprotein
cardiovascular disease
coronary artery disease
type 2 diabetes
small, dense LDL
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
Collaborators: name: Essex Pharma GmbH
First posted: 2011-06-28
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: baseline and 6 weeks
Secondary outcomes:
measure: Change of the concentrations of Total Cholesterol
timeFrame: baseline and 6 weeks
measure: Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol
timeFrame: baseline and 6 weeks
measure: Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol
timeFrame: baseline and 6 weeks
measure: Change of the concentrations of triglycerides
timeFrame: baseline and 6 weeks
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Institut für Stoffwechselforschung
city: Villingen-.Schwenningen
country: Germany
facility: Stephan Jacob, MD
Study officials:
affiliation: University Hospital Freiburg
name: Karl Winkler, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Winkler K, Jacob S, Muller-Schewe T, Hoffmann MM, Konrad T. Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus. Atherosclerosis. 2012 Jan;220(1):189-93. doi: 10.1016/j.atherosclerosis.2011.10.043. Epub 2011 Nov 9.