Metabolic Syndrome
Conditions
Keywords
triglycerides, hypertension, low hdl, obesity
Brief summary
To determine whether the combination of ezetimibe and simvastatin improves biomarkers of atherothrombosis compared to simvastatin alone in patients with the metabolic syndrome.
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.
Interventions
DRUGsimvastatin
Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied.
Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.
Sponsors
Merck Sharp & Dohme LLC
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | 6 weeks | Measured using whole blood flow cytometry |
Secondary
| Measure | Time frame |
|---|---|
| Biomarkers of Inflammation | 6 weeks |
Countries
United States
Participant flow
Recruitment details
All patients have been recruited and 15 have successfully completed the study.
Pre-assignment details
Patients excluded included those unable to tolerate statin and/or ezetimibe treatment
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Simvastatin 40 mg daily
simvastatin : Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied. | 7 |
| Simvastatin/Ezetimibe Subjects will receive 6 weeks of ezetimibe/simvastatin 10/40 mg, after which atherothrombotic biomarker assessment will be studied.
ezetimibe/simvastatin : Subjects will receive 6 weeks of simvastatin 40 mg, after which atherothrombotic biomarker assessment will be studied. | 8 |
| Total | 15 |
Baseline characteristics
| Characteristic | Simvastatin/Ezetimibe | Simvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 7 Participants | 15 Participants |
| Age, Continuous | 50.5 years STANDARD_DEVIATION 12.6 | 46.3 years STANDARD_DEVIATION 6.6 | 48.5 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment United States | 8 participants | 7 participants | 15 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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
Time frame: 6 weeks
Population: Based on power calculations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin | Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | PAR 1/4 antigen | 35.4 ng/dl | Standard Deviation 5.2 |
| Simvastatin | Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | PAR 1/4 activity | 23.6 ng/dl | Standard Deviation 4.3 |
| Simvastatin/Ezetimibe | Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | PAR 1/4 antigen | 34.5 ng/dl | Standard Deviation 5.4 |
| Simvastatin/Ezetimibe | Ex Vivo Effects of Treatment With Vytorin Versus Zocor for 6 Weeks on Platelet Alpha Thrombin PAR-1 Receptor Expression | PAR 1/4 activity | 22.5 ng/dl | Standard Deviation 6.2 |
Secondary
Biomarkers of Inflammation
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin | Biomarkers of Inflammation | CRP | 3.51 mg/dl | Standard Deviation 0.48 |
| Simvastatin | Biomarkers of Inflammation | IL-6 | 1.24 mg/dl | Standard Deviation 0.12 |
| Simvastatin/Ezetimibe | Biomarkers of Inflammation | CRP | 3.57 mg/dl | Standard Deviation 0.34 |
| Simvastatin/Ezetimibe | Biomarkers of Inflammation | IL-6 | 1.33 mg/dl | Standard Deviation 0.21 |