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

Metabolic Syndrome Clinical Trial

— Merck-123  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00988364
• Other study ID #: H-20169
• Secondary ID: MK0653A
• Status: Completed
• Phase: Phase 4
• Start date: March 2007
• Est. completion date: February 2008

Study information

• Verified date: November 2023
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & Publications (20)

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	L5 Concentration in Metabolic Syndrome Patients	Patient's blood samples were collected before treatment. L5 were purified by ultracentrifugation then FPLC. Quantification analysis will indicate the L5 concentration (mg/dL) per group.	0 months, at the start
Secondary	L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients	Patient's blood samples were collected at the corresponding time point for L5 purification. L5 quantification and characterization were investigated with chemical analysis, proteomics and in-vitro cell signaling analysis. Final data analysis will determine total L5 concentration (mg/dL).	3 months