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

Primary Purpose

Diabetes Mellitus Type 2, Hypercholesterolemia

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
ezetimibe
simvastatin
Ezetimibe 10/Simvastatin 20
Sponsored by
University Hospital Freiburg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus Type 2 focused on measuring atherogenic lipoprotein, cardiovascular disease, coronary artery disease, type 2 diabetes, small, dense LDL

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut für Stoffwechselforschung
  • Stephan Jacob, MD

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Ezetimibe 10mg/d

Simvastatin 20 mg per day

Ezetimibe 10 mg/d and Simvastatin 20mg/d

Arm Description

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

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

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

Outcomes

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
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
Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol
Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol
Change of the concentrations of triglycerides

Full Information

First Posted
June 23, 2011
Last Updated
June 18, 2012
Sponsor
University Hospital Freiburg
Collaborators
Essex Pharma GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01384058
Brief Title
Effect of Ezetimibe or Simvastatin or Both on Low Densitiy Lipoprotein -Subfractions in Patients With Type 2 Diabetes
Acronym
EZE
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

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
June 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Freiburg
Collaborators
Essex Pharma GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus Type 2, Hypercholesterolemia
Keywords
atherogenic lipoprotein, cardiovascular disease, coronary artery disease, type 2 diabetes, small, dense LDL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ezetimibe 10mg/d
Arm Type
Active Comparator
Arm Description
intake of ezetimibe 10mg per day for six weeks after wash-out
Arm Title
Simvastatin 20 mg per day
Arm Type
Active Comparator
Arm Description
intake of simvastatin 20 mg per day for six weeks after wash-out
Arm Title
Ezetimibe 10 mg/d and Simvastatin 20mg/d
Arm Type
Active Comparator
Arm Description
intake of ezetimibe 10 mg and simvastatin 20 mg per day for six weeks after wash-out
Intervention Type
Drug
Intervention Name(s)
ezetimibe
Other Intervention Name(s)
Ezetrol 10 mg
Intervention Description
ezetimibe 10 mg per day for six weeks
Intervention Type
Drug
Intervention Name(s)
simvastatin
Other Intervention Name(s)
Zocor MSD
Intervention Description
Simvastatin 20 mg per day for six weeks
Intervention Type
Drug
Intervention Name(s)
Ezetimibe 10/Simvastatin 20
Other Intervention Name(s)
Inegy 10/20
Intervention Description
Ezetimibe 10mg/Simvastatin 20mg per day for six weeks
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
baseline and 6 weeks
Secondary Outcome Measure Information:
Title
Change of the concentrations of Total Cholesterol
Time Frame
baseline and 6 weeks
Title
Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol
Time Frame
baseline and 6 weeks
Title
Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol
Time Frame
baseline and 6 weeks
Title
Change of the concentrations of triglycerides
Time Frame
baseline and 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karl Winkler, MD
Organizational Affiliation
University Hospital Freiburg
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut für Stoffwechselforschung
City
Frankfurt
ZIP/Postal Code
60322
Country
Germany
Facility Name
Stephan Jacob, MD
City
Villingen-.Schwenningen
ZIP/Postal Code
78048
Country
Germany

12. IPD Sharing Statement

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

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