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

This study has been completed.
Sponsor:
Collaborator:
Essex Pharma GmbH
Information provided by (Responsible Party):
Karl Winkler, University Hospital Freiburg
ClinicalTrials.gov Identifier:
NCT01384058
First received: June 23, 2011
Last updated: June 18, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus Type 2
Hypercholesterolemia
Drug: ezetimibe
Drug: simvastatin
Drug: Ezetimibe 10/Simvastatin 20
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital Freiburg:

Primary Outcome Measures:
  • 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 [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Change of the concentrations of Total Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
  • Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
  • Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
  • Change of the concentrations of triglycerides [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: November 2007
Study Completion Date: June 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ezetimibe 10mg/d
intake of ezetimibe 10mg per day for six weeks after wash-out
Drug: ezetimibe
ezetimibe 10 mg per day for six weeks
Other Name: Ezetrol 10 mg
Active Comparator: Simvastatin 20 mg per day
intake of simvastatin 20 mg per day for six weeks after wash-out
Drug: simvastatin
Simvastatin 20 mg per day for six weeks
Other Name: Zocor MSD
Active Comparator: Ezetimibe 10 mg/d and Simvastatin 20mg/d
intake of ezetimibe 10 mg and simvastatin 20 mg per day for six weeks after wash-out
Drug: Ezetimibe 10/Simvastatin 20
Ezetimibe 10mg/Simvastatin 20mg per day for six weeks
Other Name: Inegy 10/20

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01384058

Locations
Germany
Institut für Stoffwechselforschung
Frankfurt, Germany, 60322
Stephan Jacob, MD
Villingen-.Schwenningen, Germany, 78048
Sponsors and Collaborators
University Hospital Freiburg
Essex Pharma GmbH
Investigators
Principal Investigator: Karl Winkler, MD University Hospital Freiburg
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Karl Winkler, MD, Prof. Dr. med., Kommissarischer Ärztlicher Direktor, University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT01384058     History of Changes
Other Study ID Numbers: 442006, 2006-005906-30
Study First Received: June 23, 2011
Last Updated: June 18, 2012
Health Authority: Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital Freiburg:
atherogenic lipoprotein
cardiovascular disease
coronary artery disease
type 2 diabetes
small, dense LDL

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypercholesterolemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Simvastatin
Ezetimibe
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014