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

NCT01384058 | Completed Phase 4 DMC

• 2 other identifiers: 4420062006-005906-30
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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.

Conditions

Diabetes Mellitus Type 2; Hypercholesterolemia

Keywords

atherogenic lipoprotein; cardiovascular disease; coronary artery disease; type 2 diabetes; small, dense LDL

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (3)

Ezetimibe 10mg/d

ACTIVE COMPARATOR

intake of ezetimibe 10mg per day for six weeks after wash-out

Drug: ezetimibe

Simvastatin 20 mg per day

ACTIVE COMPARATOR

intake of simvastatin 20 mg per day for six weeks after wash-out

Drug: simvastatin

Ezetimibe 10 mg/d and Simvastatin 20mg/d

ACTIVE COMPARATOR

intake of ezetimibe 10 mg and simvastatin 20 mg per day for six weeks after wash-out

Drug: Ezetimibe 10/Simvastatin 20

Interventions

ezetimibe DRUG

ezetimibe 10 mg per day for six weeks

Also known as: Ezetrol 10 mg

Ezetimibe 10mg/d

simvastatin DRUG

Simvastatin 20 mg per day for six weeks

Also known as: Zocor MSD

Simvastatin 20 mg per day

Ezetimibe 10/Simvastatin 20 DRUG

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

Also known as: Inegy 10/20

Ezetimibe 10 mg/d and Simvastatin 20mg/d

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Freiburg: lead
• Essex Pharma GmbH: collaborator

Study Sites (2)

Institut für Stoffwechselforschung

Frankfurt, Germany, 60322, Germany

Location

Stephan Jacob, MD

Villingen-Schwenningen, Germany, 78048, Germany

Location

Related Publications (22)

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• Winkler K, Friedrich I, Baumstark MW, Wieland H, März W 2002 Pioglitazone reduces atherogenic dense low density lipoprotein (LDL) particles in patients with type 2 diabetes mellitus. Br J Diabetes Vasc Dis 2:143-148

  BACKGROUND

• Winkler K, Konrad T, Fullert S, Friedrich I, Destani R, Baumstark MW, Krebs K, Wieland H, Marz W. Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. Diabetes Care. 2003 Sep;26(9):2588-94. doi: 10.2337/diacare.26.9.2588.

  PMID: 12941723 BACKGROUND

• 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.

  PMID: 22115011 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypercholesterolemia; Cardiovascular Diseases; Coronary Artery Disease; Cerebral Palsy

Interventions

Ezetimibe; Simvastatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Coronary Disease; Myocardial Ischemia; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Karl Winkler, MD

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Prof. Dr. med., Kommissarischer Ärztlicher Direktor

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 28, 2011
• Study Start: November 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: June 1, 2010
• Last Updated: June 19, 2012

Record last verified: 2012-06

Locations

DE (2)