Merck-123: Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 a Subfraction of LDL in Patients With Metabolic Syndrome.

Sponsor

Baylor College of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT00988364

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arms

11.1

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Metabolic Syndrome	Drug: Simvastatin Drug: Vytorin Drug: Placebo Drug: Ezetimibe	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Feb 1, 2008

Actual Study Completion Date :

Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Ezetimibe Randomly chosen participants will receive ezetimibe 10mg daily for 3 months.	Drug: Ezetimibe Ezetimibe 10mg daily for 3 months. Other Names: Zetia
Active Comparator: Simvastatin Randomly chosen participants will receive Simvastatin 20mg daily for 3 months.	Drug: Simvastatin Simvastatin 20mg daily for 3 months. Other Names: Zocor
Active Comparator: Vytorin Randomly chosen participants will receive Vytorin 20/10mg daily for 3 months.	Drug: Vytorin Vytorin 20/10mg daily for 3 months. Other Names: Ezetimibe/Simvastatin
Placebo Comparator: Placebo Randomly chosen participants will receive Placebo tab 1 daily for 3 months.	Drug: Placebo Placebo one tablet daily times 3 months. Other Names: Control

Outcome Measures

Primary Outcome Measures

To identify the common factor for L5 prevalence in Metabolic Syndrome patients. [3 months]
Patient's blood samples will be collected at the corresponding time points. L5 will be purified by ultracentrifugation, FPLC. Quantification analysis will indicate the L5 concentration, lipoprotein distribution profile in each participant."

Secondary Outcome Measures

To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome. [3 months]
Patient's blood samples will be collected at each corresponding time point for L5 purification. L5 quantification and characterization will be investigated with chemical analysis, proteomics and in-vitro cell signaling analysis. Final data analysis will determine total L5 concentration, lipid/lipoprotein profile difference before and after treatment, and its cell signaling impact in endothelial/smooth muscle cell model.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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