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

Hypercholesterolemia Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01384058
• Other study ID #: 442006
• Secondary ID: 2006-005906-30
• Status: Completed
• Phase: Phase 4
• First received: June 23, 2011
• Last updated: June 18, 2012
• Start date: November 2007
• Est. completion date: June 2010

Study information

• Verified date: June 2012
• Source: University Hospital Freiburg
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2
• Hypercholesterolemia

Intervention

Drug:
• ezetimibe
ezetimibe 10 mg per day for six weeks
• simvastatin
Simvastatin 20 mg per day for six weeks
• Ezetimibe 10/Simvastatin 20
Ezetimibe 10mg/Simvastatin 20mg per day for six weeks

Locations

Country	Name	City	State
Germany	Institut für Stoffwechselforschung	Frankfurt
Germany	Stephan Jacob, MD	Villingen-.Schwenningen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Freiburg	Essex Pharma GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (21)

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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. — View Citation

Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990 Aug;82(2):495-506. — View Citation

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Blake GJ, Otvos JD, Rifai N, Ridker PM. Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation. 2002 Oct 8;106(15):1930-7. — View Citation

Charman RC, Matthews LB, Braeuler C. Nicotinic acid in the treatment of hypercholesterolemia. A long term study. Angiology. 1972 Jan;23(1):29-35. — View Citation

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. — View Citation

DiPalma JR, Thayer WS. Use of niacin as a drug. Annu Rev Nutr. 1991;11:169-87. Review. — View Citation

Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996 Sep 18;276(11):875-81. — View Citation

Griffin BA, Freeman DJ, Tait GW, Thomson J, Caslake MJ, Packard CJ, Shepherd J. Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis. 1994 Apr;106(2):241-53. — View Citation

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. — View Citation

Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Després JP. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Circulation. 1997 Jan 7;95(1):69-75. — View Citation

Nigon F, Lesnik P, Rouis M, Chapman MJ. Discrete subspecies of human low density lipoproteins are heterogeneous in their interaction with the cellular LDL receptor. J Lipid Res. 1991 Nov;32(11):1741-53. — View Citation

Nordestgaard BG, Nielsen LB. Atherosclerosis and arterial influx of lipoproteins. Curr Opin Lipidol. 1994 Aug;5(4):252-7. Review. — View Citation

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. — View Citation

Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, Hennekens CH. A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA. 1996 Sep 18;276(11):882-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change of the concentrations of Total Cholesterol		baseline and 6 weeks	No
Secondary	Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol		baseline and 6 weeks	No
Secondary	Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol		baseline and 6 weeks	No
Secondary	Change of the concentrations of triglycerides		baseline and 6 weeks	No