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

Condition(s) targeted: Metabolic Syndrome

Intervention: Simvastatin (Drug); Vytorin (Drug); Placebo (Drug); Ezetimibe (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Baylor College of Medicine

Official(s) and/or principal investigator(s):
Chu-Huang Chen, M.D., Ph.D., Principal Investigator, Affiliation: Baylor College of Medicine
Christie Ballantyne, M.D., Study Director, Affiliation: Baylor College of Medicine

Overall contact:
Sarah L Liscum, MPH, Phone: 713-798-6476, Email: slliscum@bcm.tmc.edu

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.

Official title: Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 in Patients With Metabolic Syndrome

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Factorial Assignment, Efficacy Study

Primary outcome: To identify the common factor for L5 prevalence in Metabolic Syndrome patients.

Secondary outcome: To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Sarah L Liscum, MPH, Phone: 713-798-6476, Email: slliscum@bcm.tmc.edu

Baylor College of Medicine, Houston, Texas 77030, United States

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Starting date: October 2009
Ending date: July 2010
Last updated: October 5, 2009