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

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.

Study Type: Interventional

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

Study Primary Completion Date: April 2010

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.

Intervention(s) in this Clinical Trial

• Drug: Simvastatin
  • Simvastatin 20mg daily for 3 months.
• Drug: Vytorin
  • Vytorin 20/10mg daily for 3 months.
• Drug: Placebo
  • Placebo one tablet daily times 3 months.
• Drug: Ezetimibe
  • Ezetimibe 10mg daily for 3 months.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Ezetimibe
  • Randomly chosen participants will receive ezetimibe 10mg daily for 3 months.
• Active Comparator: Simvastatin
  • Randomly chosen participants will receive Simvastatin 20mg daily for 3 months.
• Active Comparator: Vytorin
  • Randomly chosen participants will receive Vytorin 20/10mg daily for 3 months.
• Placebo Comparator: Placebo
  • Randomly chosen participants will receive Placebo tab 1 daily for 3 months.

Primary Measures

• To identify the common factor for L5 prevalence in Metabolic Syndrome patients.
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome.
  • Time Frame: 3 months
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Baylor College of Medicine

Overall Clinical Trial Officials and Contacts

Chu-Huang Chen, M.D., Ph.D. Principal Investigator Baylor College of Medicine  

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

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00988364

Study ID Number: Merck-123

ClinicalTrials.gov Identifier: NCT00988364

Health Authority: United States: Institutional Review Board