Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

Study Overview
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Brief Summary
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To determine whether the combination of ezetimibe and simvastatin improves biomarkers of atherothrombosis compared to simvastatin alone in patients with the metabolic syndrome.

Detailed Description
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To assess the ex vivo effects of ezetimibe/simvastatin (E/S) (Vytorin 10/40mg) and simvastatin (S) (Zocor 40mg) on platelet and inflammation biomarkers in patients with documented metabolic syndrome. To compare platelet-related effects including PAR-1 receptor inhibition of E/S with those of the established anti-platelet agents including aspirin, clopidogrel, intravenous and oral glycoprotein IIb/IIIa inhibitors. To determine whether the addition of ezetimibe will yield extra protection beyond lipid modulation in the reduction of inflammation and platelet activation.

Official Title
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The Effects of Ezetimibe/Simvastatin Versus Simvastatin Alone on Platelet and Inflammatory Biomarkers in Patients With the Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: simvastatin
* Drug: ezetimibe/simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women greater than or equal to 21 years of age Diagnosis of metabolic syndrome. We defined the presence of metabolic syndrome based on the US National Cholesterol Education Program's Adult Treatment Panel III guidelines. Specifically, metabolic syndrome will be diagnosed and documented when 3 of the following 5 characteristics will be present: abdominal obesity, given as waist circumference for men > 102 cm, and for women > 88 cm triglycerides > 150 mg/dL HDL cholesterol < 40 mg/dL for men, and < 50 mg/dL for women blood pressure > 130/85 mm Hg fasting glucose > 100 mg/dL Exclusion Criteria: Patients will be excluded for a history of bleeding diathesis drug or alcohol abuse prothrombin time greater than 1.5 times control platelet count < 100,000/mm3 hematocrit < 25% creatinine > 4.0 mg/dl surgery or angioplasty performed within 3 months or planned for the future history of gastrointestinal or other bleeding history of drug-induced disorders trauma, cancer, rheumatic diseases, coronary artery disease or stroke Patients participating in other investigational drug trials within one month of completion will be also excluded Patients treated with intravenous platelet glycoprotein IIb/IIIa inhibitors or thienopyridines, within past 6 months Patients treated with statins or aspirin within past four weeks

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: simvastatin<br>Simvastatin 40 mg daily | Drug: simvastatin<br>* Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.<br>* Other names: zocor;|
| Active Comparator: simvastatin/ezetimibe<br>Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied. | Drug: ezetimibe/simvastatin<br>* Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.<br>* Other names: vytorin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | Measured using whole blood flow cytometry | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers of Inflammation |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triglycerides, hypertension, low hdl, obesity