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

Information source: University Hospital Freiburg
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Diabetes Mellitus Type 2; Hypercholesterolemia

Intervention: ezetimibe (Drug); simvastatin (Drug); Ezetimibe 10/Simvastatin 20 (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: University Hospital Freiburg

Official(s) and/or principal investigator(s):
Karl Winkler, MD, Principal Investigator, Affiliation: University Hospital Freiburg

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

Locations and Contacts

Institut für Stoffwechselforschung, Frankfurt 60322, Germany

Stephan Jacob, MD, Villingen-.Schwenningen 78048, Germany

Additional Information

Related publications:

Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998 Jul 23;339(4):229-34.

Reaven GM, Chen YD, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest. 1993 Jul;92(1):141-6.

Austin MA, Edwards KL. Small, dense low density lipoproteins, the insulin resistance syndrome and noninsulin-dependent diabetes. Curr Opin Lipidol. 1996 Jun;7(3):167-71. Review.

Winkler K, Abletshauser C, Hoffmann MM, Friedrich I, Baumstark MW, Wieland H, März W. Effect of fluvastatin slow-release on low density lipoprotein (LDL) subfractions in patients with type 2 diabetes mellitus: baseline LDL profile determines specific mode of action. J Clin Endocrinol Metab. 2002 Dec;87(12):5485-90.

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Dejager S, Bruckert E, Chapman MJ. Dense low density lipoprotein subspecies with diminished oxidative resistance predominate in combined hyperlipidemia. J Lipid Res. 1993 Feb;34(2):295-308.

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ALTSCHUL R, HOFFER A, STEPHEN JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955 Feb;54(2):558-9.

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Winkler K, Weltzien P, Friedrich I, Schmitz H, Nickell HH, Hauck P, Hoffmann MM, Baumstark MW, Wieland H, März W. Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL. Exp Clin Endocrinol Diabetes. 2004 May;112(5):241-7.

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

Winkler K, Konrad T, Füllert S, Friedrich I, Destani R, Baumstark MW, Krebs K, Wieland H, März 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.

Starting date: November 2007
Last updated: June 18, 2012

Page last updated: August 23, 2015

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