Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 a Subfraction of LDL in Patients With Metabolic Syndrome. - Full Text View

Sponsor:	Baylor College of Medicine
Collaborator:	Merck
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00988364

Purpose

The purpose of this study is:

To identify the common factor for L5 prevalence in patients with Metabolic Syndrome.
To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome patients.

Condition	Intervention	Phase
Metabolic Syndrome	Drug: Simvastatin Drug: Vytorin Drug: Placebo Drug: Ezetimibe	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Treatment
Official Title:	Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 in Patients With Metabolic Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Metabolic Syndrome

Drug Information available for: Simvastatin Ezetimibe Vytorin

U.S. FDA Resources

Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:

To identify the common factor for L5 prevalence in Metabolic Syndrome patients. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	October 2009
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Ezetimibe Randomly chosen participants will receive ezetimibe 10mg daily for 3 months.	Drug: Ezetimibe Ezetimibe 10mg daily for 3 months.
Active Comparator: Simvastatin Randomly chosen participants will receive Simvastatin 20mg daily for 3 months.	Drug: Simvastatin Simvastatin 20mg daily for 3 months.
Active Comparator: Vytorin Randomly chosen participants will receive Vytorin 20/10mg daily for 3 months.	Drug: Vytorin Vytorin 20/10mg daily for 3 months.
Placebo Comparator: Placebo Randomly chosen participants will receive Placebo tab 1 daily for 3 months.	Drug: Placebo Placebo one tablet daily times 3 months.

Detailed Description:

Epidemiological evidence indicates that metabolic syndrome (MS) is a strong predisposing condition for atherosclerosis. Elevation of plasma low-density lipoprotein (LDL) cholesterol(LDL-C) concentration is the most important risk factor for atherosclerosis; however, LDL-C elevation is not a criterion for metabolic syndrome, raising the question of LDL's role in the syndrome's association with atherosclerosis. L5, a highly electronegative and mildly oxidized LDL subfraction that we recently isolated from hypercholesterolemic human plasma, may provide a key to answering this question. In cultured vascular endothelial cells (EC), L5 inhibits proliferation and induces apoptosis and monocyte-EC adhesion. In our preliminary studies, L5 could also be detected in patients with MS without elevated LDL-C. Because other LDL subfractions were harmless to EC, the presence of MS-L5 prompted us to hypothesize that the atherogenic role of LDL is not solely determined by plasma LDL-C concentration, but more importantly, by its composition. The proposed study is designed to test this hypothesis. The first question we will address is what lipid factor determines the prevalence of L5 in MS.

Subsequently, we will examine whether treatment with selected medicines can effectively reduce L5 in MS patients by correcting the factor favorable for L5 formation.

We are in the process of identifying the active components of L5 to fully characterize the atherogenic role of L5 in MS,. In the current proposal, we focus our interest on the efficacy of Ezetimibe, Simvastatin, and Vytorin in reducing L5 from the plasma of MS patients.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Participants who meet 3 or more of the 5 criteria specified in the ATPIII guidelines will be recruited.
The 5 criteria are:
1. abdominal obesity (men>40 inches, women >35 inches);
2. TG> 150mg/dL;
3. low HDL-C (men < 40mg/dL, women < 50 mg/dL);
4. high blood pressure (>or=130/>or=85 mmHg);
5. fasting glucose > or = 110mg/dL.
People with different ethnic backgrounds will be included.

Exclusion Criteria:

symptomatic coronary artery disease
peripheral vascular disease
cerebral ischemia (stroke)
smoking
hypothyroidism
kidney diseases
consumption of antioxidation supplements/drugs or use of lipid-lowering drugs in the last 3 months
women who are pregnant, nursing, or planning to become pregnant

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00988364

Contacts

Contact: Sarah L Liscum, MPH

713-798-6476

slliscum@bcm.tmc.edu

Locations

United States, Texas
Baylor College of Medicine	Active, not recruiting
Houston, Texas, United States, 77030

Sponsors and Collaborators

Baylor College of Medicine

Merck

Investigators

Principal Investigator:	Chu-Huang Chen, M.D., Ph.D.	Baylor College of Medicine
Study Director:	Christie Ballantyne, M.D.	Baylor College of Medicine

More Information

Publications:

Avogaro P, Cazzolato G, Bittolo-Bon G. Some questions concerning a small, more electronegative LDL circulating in human plasma. Atherosclerosis. 1991 Nov;91(1-2):163-71.

Ballantyne CM, Houri J, Notarbartolo A, Melani L, Lipka LJ, Suresh R, Sun S, LeBeaut AP, Sager PT, Veltri EP; Ezetimibe Study Group. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation. 2003 May 20;107(19):2409-15. Epub 2003 Apr 28.

Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, Sharrett AR. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004 Feb 24;109(7):837-42. Epub 2004 Feb 2.

Chan DC, Watts GF, Barrett PH, Mamo JC, Redgrave TG. Markers of triglyceride-rich lipoprotein remnant metabolism in visceral obesity. Clin Chem. 2002 Feb;48(2):278-83.

Chen CH, Jiang T, Yang JH, Jiang W, Lu J, Marathe GK, Pownall HJ, Ballantyne CM, McIntyre TM, Henry PD, Yang CY. Low-density lipoprotein in hypercholesterolemic human plasma induces vascular endothelial cell apoptosis by inhibiting fibroblast growth factor 2 transcription. Circulation. 2003 Apr 29;107(16):2102-8. Epub 2003 Apr 14.

Chen CH, Pace PW, Karakoc ND, Lu J, Chen HH, Henry PD, Pownall HJ Foreyt JP, Ballantyne CM, Yang CY. Effective reduction of novel atherogenic LDL subfraction by atorvastatin in patients with hypercholesteremia. J AM Coll Cardiol. 2004:43(suppl A):486A (Abstract)

Chappey B, Myara I, Benoit MO, Mazière C, Mazière JC, Moatti N. Characteristics of ten charge-differing subfractions isolated from human native low-density lipoproteins (LDL). No evidence of peroxidative modifications. Biochim Biophys Acta. 1995 Dec 7;1259(3):261-70.

De Castellarnau C, Sánchez-Quesada JL, Benítez S, Rosa R, Caveda L, Vila L, Ordóñez-Llanos J. Electronegative LDL from normolipemic subjects induces IL-8 and monocyte chemotactic protein secretion by human endothelial cells. Arterioscler Thromb Vasc Biol. 2000 Oct;20(10):2281-7.

Demuth K, Myara I, Chappey B, Vedie B, Pech-Amsellem MA, Haberland ME, Moatti N. A cytotoxic electronegative LDL subfraction is present in human plasma. Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):773-83.

Kleinman Y, Krul ES, Burnes M, Aronson W, Pfleger B, Schonfeld G. Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J Lipid Res. 1988 Jun;29(6):729-43.

La Belle M, Blanche PJ, Krauss RM. Charge properties of low density lipoprotein subclasses. J Lipid Res. 1997 Apr;38(4):690-700.

Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003 May 1;23(5):853-8. Epub 2003 Mar 13.

Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-874.

Sánchez-Quesada JL, Benítez S, Ordóñez-Llanos J. Electronegative low-density lipoprotein. Curr Opin Lipidol. 2004 Jun;15(3):329-35. Review.

Sevanian A, Bittolo-Bon G, Cazzolato G, Hodis H, Hwang J, Zamburlini A, Maiorino M, Ursini F. LDL- is a lipid hydroperoxide-enriched circulating lipoprotein. J Lipid Res. 1997 Mar;38(3):419-28.

Steinberg D. Lewis A. Conner Memorial Lecture. Oxidative modification of LDL and atherogenesis. Circulation. 1997 Feb 18;95(4):1062-71. Review. No abstract available.

Simons L, Tonkon M, Masana L, Maccubbin D, Shah A, Lee M, Gumbiner B. Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome. Curr Med Res Opin. 2004 Sep;20(9):1437-45.

van Heek M, Austin TM, Farley C, Cook JA, Tetzloff GG, Davis HR. Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters. Diabetes. 2001 Jun;50(6):1330-5.

Yang CY, Raya JL, Chen HH, Chen CH, Abe Y, Pownall HJ, Taylor AA, Smith CV. Isolation, characterization, and functional assessment of oxidatively modified subfractions of circulating low-density lipoproteins. Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1083-90. Epub 2003 Apr 10.

Yang CY, Chen HH, Huang MT, Raya JL, Yang JH, Chen CH, Gaubatz JW, Pownall HJ, Taylor AA, Ballantyne CM, Jenniskens FA, Smith CV. Pro-apoptotic low-density lipoprotein subfractions in type II diabetes. Atherosclerosis. 2007 Aug;193(2):283-91. Epub 2006 Oct 9.

Responsible Party:	Chu-Huang Chen, M.D., Ph.D., Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00988364 History of Changes
Other Study ID Numbers:	Merck-123, MK0653A
Study First Received:	October 1, 2009
Last Updated:	October 5, 2009
Health Authority:	United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:

Metabolic Syndrome
LDL subfraction L5
The reduction of LDL Chol in patients with Metabolic Syndrome
The prevalence of L5 in patients with Metabolic Syndrome
The reduction of L5 subfraction in patients with Metabolic Syndrome

Additional relevant MeSH terms:

Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Simvastatin
Ezetimibe
Hypolipidemic Agents

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012