Clinical trial NCT00988364: Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 a Subfraction of LDL in Patients With Metabolic Syndrome.
Official title: Effects of Ezetimibe, Simvastatin, and Vytorin on Reducing L5 in Patients With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metabolic Syndrome
Keywords: 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
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-10-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, placebo-controlled clinical trial with 4 arms
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: L5 Concentration in Metabolic Syndrome Patients
timeFrame: 0 months, at the start
Secondary outcomes:
measure: L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients
timeFrame: 3 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Chu-Huang Chen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Christie Ballantyne, M.D.
role: STUDY_DIRECTOR
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