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

Baylor College of Medicine

Status and phase: Completed; Phase 4

Conditions: Metabolic Syndrome

Treatments: Drug: Placebo; Drug: Vytorin; Drug: Simvastatin; Drug: Ezetimibe

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00988364

H-20169

MK0653A

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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:

  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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 4 patient groups, including a placebo group

Ezetimibe

Active Comparator group

Description:

Randomly chosen participants will receive ezetimibe 10mg daily for 3 months.

Treatment:

Drug: Ezetimibe

Simvastatin

Active Comparator group

Description:

Randomly chosen participants will receive Simvastatin 20mg daily for 3 months.

Treatment:

Drug: Simvastatin

Vytorin

Active Comparator group

Description:

Randomly chosen participants will receive Vytorin 20/10mg daily for 3 months.

Treatment:

Drug: Vytorin

Placebo

Placebo Comparator group

Description:

Randomly chosen participants will receive Placebo tab 1 daily for 3 months.

Treatment:

Drug: Placebo