Simvastatin With or Without Ezetimibe and Atherothrombotic Biomarker Assessment

The Effects of Ezetimibe/Simvastatin Versus Simvastatin Alone on Platelet and Inflammatory Biomarkers in Patients With the Metabolic Syndrome

To determine whether the combination of ezetimibe and simvastatin improves biomarkers of atherothrombosis compared to simvastatin alone in patients with the metabolic syndrome.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: simvastatin; Drug: ezetimibe/simvastatin

Detailed Description

1. To assess the ex vivo effects of ezetimibe/simvastatin (E/S) (Vytorin 10/40mg) and simvastatin (S) (Zocor 40mg) on platelet and inflammation biomarkers in patients with documented metabolic syndrome.
2. To compare platelet-related effects including PAR-1 receptor inhibition of E/S with those of the established anti-platelet agents including aspirin, clopidogrel, intravenous and oral glycoprotein IIb/IIIa inhibitors.
3. To determine whether the addition of ezetimibe will yield extra protection beyond lipid modulation in the reduction of inflammation and platelet activation.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
    • Baltimore, Maryland, United States, 21201
      • VA Maryland Health Care System
    • Baltimore, Maryland, United States, 21202
      • University of Maryland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women greater than or equal to 21 years of age

2. Diagnosis of metabolic syndrome. We defined the presence of metabolic syndrome based on the US National Cholesterol Education Program's Adult Treatment Panel III guidelines. Specifically, metabolic syndrome will be diagnosed and documented when 3 of the following 5 characteristics will be present:

   • abdominal obesity, given as waist circumference for men > 102 cm, and for women > 88 cm
   • triglycerides > 150 mg/dL
   • HDL cholesterol < 40 mg/dL for men, and < 50 mg/dL for women
   • blood pressure > 130/85 mm Hg
   • fasting glucose > 100 mg/dL

Exclusion Criteria:

1. Patients will be excluded for a history of bleeding diathesis
2. drug or alcohol abuse
3. prothrombin time greater than 1.5 times control
4. platelet count < 100,000/mm3
5. hematocrit < 25%
6. creatinine > 4.0 mg/dl
7. surgery or angioplasty performed within 3 months or planned for the future
8. history of gastrointestinal or other bleeding
9. history of drug-induced disorders
10. trauma, cancer, rheumatic diseases, coronary artery disease or stroke
11. Patients participating in other investigational drug trials within one month of completion will be also excluded
12. Patients treated with intravenous platelet glycoprotein IIb/IIIa inhibitors or thienopyridines, within past 6 months
13. Patients treated with statins or aspirin within past four weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: simvastatin; Simvastatin 40 mg daily	Drug: simvastatin; Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.; Other Names: zocor
ACTIVE_COMPARATOR: simvastatin/ezetimibe; Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.	Drug: ezetimibe/simvastatin; Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.; Other Names: vytorin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression	Measured using whole blood flow cytometry	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Biomarkers of Inflammation	6 weeks

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: MICHAEL MILLER, MD, University of Maryland, College Park; Study Director: VICTOR L. Serebruany, MD, PhD, President, HeartDrug Research LLC

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (ACTUAL): November 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: January 7, 2009
• First Submitted That Met QC Criteria: January 8, 2009
• First Posted (ESTIMATE): January 9, 2009

Study Record Updates

• Last Update Posted (ACTUAL): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: obesity; hypertension; triglycerides; low hdl
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
• Other Study ID Numbers: HP-00040970; MSP-JV IISP #32031