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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Vytorin
* Drug: Placebo
* Drug: Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who meet 3 or more of the 5 criteria specified in the ATPIII guidelines will be recruited. The 5 criteria are: abdominal obesity (men>40 inches, women >35 inches); TG> 150mg/dL; low HDL-C (men < 40mg/dL, women < 50 mg/dL); high blood pressure (>or=130/>or=85 mmHg); 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, placebo-controlled clinical trial with 4 arms
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ezetimibe<br>Randomly chosen participants will receive ezetimibe 10mg daily for 3 months. | Drug: Ezetimibe<br>* Ezetimibe 10mg daily for 3 months.<br>* Other names: Zetia;|
| Active Comparator: Simvastatin<br>Randomly chosen participants will receive Simvastatin 20mg daily for 3 months. | Drug: Simvastatin<br>* Simvastatin 20mg daily for 3 months.<br>* Other names: Zocor;|
| Active Comparator: Vytorin<br>Randomly chosen participants will receive Vytorin 20/10mg daily for 3 months. | Drug: Vytorin<br>* Vytorin 20/10mg daily for 3 months.<br>* Other names: Ezetimibe/Simvastatin;|
| Placebo Comparator: Placebo<br>Randomly chosen participants will receive Placebo tab 1 daily for 3 months. | Drug: Placebo<br>* Placebo one tablet daily times 3 months.<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| L5 Concentration in Metabolic Syndrome Patients | Patient's blood samples were collected before treatment. L5 were purified by ultracentrifugation then FPLC. Quantification analysis will indicate the L5 concentration (mg/dL) per group. | 0 months, at the start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | Patient's blood samples were collected at the corresponding time point for L5 purification. L5 quantification and characterization were investigated with chemical analysis, proteomics and in-vitro cell signaling analysis. Final data analysis will determine total L5 concentration (mg/dL). | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic Syndrome, LDL subfraction L5, The reduction of LDL in patients with Metabolic Syndrome, The prevalence of L5 in patients with Metabolic Syndrome, The reduction of L5 in patients with Metabolic Syndrome