Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-09-30

Study Completion Date

2008-02-29

Brief Summary

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Multiple clinical trials, using 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins), have shown benefit in the primary and secondary prevention of atherosclerotic complications. However, till now, there is an incomplete understanding of all the mechanisms of the biologic effects of statins beyond LDL cholesterol (LDL-C) reduction, but there is accumulating evidence that the Rho-GTP/Rho-Kinase pathway (Rho/Rho-K) plays an important role and may be a strategic therapeutic target in cardiovascular diseases. With similar LDL-C reduction ability, the availability of Ezetimibe offers the potential to begin to address the question whether some of the benefits conferred by statins may accrue independently of their effects on LDL-C lowering. A better understanding of the role of the Rho/Rho-kinase signaling pathway in the pathogenesis of atherosclerosis in human is essential. Inhibition of Rho/Rho-kinase by statins may explain some of the biological beneficial effects of statins observed in clinical trials. This study aims to translate into patients important experimental discoveries regarding the initiation of inflammation in atherosclerosis in an attempt to improve upon the present treatment of cardiovascular diseases.

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Detailed Description

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Study Design:

A single-blind controlled trial with two arms will be conducted at National Chen-Kung University Hospital (NCKUH). We will screen subjects with stable atherosclerosis to complete enrollment of 40 subjects in the study (see inclusion and exclusion criteria section below). A central pharmacist at NCKUH will randomize the patients to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) for 28 days. If the patient is already on a statin a two-week washout period will be 2 weeks prior to trial initiation.

Primary Outcomes and measurement:

The primary outcomes are the mean changes in the Rho-kinase expression and activity in leukocytes in response to 40mg or Simvastatin (n=20) or 10mg/10mg of Ezetimibe/Simvastatin (n=20) over 28 days.

Secondary Outcomes and measurement:

The secondary outcomes are the correlation between the mean changes in Rho-kinase expression and activity in leukocytes and vascular tissue with the mean changes in LDL-C, hsCRP, and BAFMD, as well as its relation with clinical characteristics.

Subjects:

Participants will be recruited from the ambulatory clinics at the NCKUH Clinic.

Inclusion Criteria:

1. Male or female subjects aged 40 to 80 years
2. Documented stable atherosclerosis by angiography or vascular ultrasound (more that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program (ATP)-III guidelines)
3. LDL-cholesterol \>100mg/dL (indication to treat with statin)
4. Written informed consent
5. Primary care physician authorization letter to participate in the study.

Exclusion criteria:

1. Inability to give consent
2. Pre-menopausal women
3. Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
4. History of LFT \>2 times the upper normal limit
5. History of myopathy / myositis or CPK \> 10 times the upper normal limit
6. CPK above normal limits at study onset
7. Any evidence of inflammatory, infectious or neoplastic disease
8. History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.

Conditions

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Atherosclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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high dose statin

40mg of Simvastatin (n=20)

Group Type EXPERIMENTAL

Simvastatin (Zocor)

Intervention Type DRUG

40mg of Simvastatin (n=20) orally per-day for 28 days

combination arm

10mg/10mg of Ezetimibe/Simvastatin (n=20)

Group Type ACTIVE_COMPARATOR

10mg/10mg of Ezetimibe/Simvastatin (Vytorin)

Intervention Type DRUG

10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days

Interventions

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Simvastatin (Zocor)

40mg of Simvastatin (n=20) orally per-day for 28 days

Intervention Type DRUG

10mg/10mg of Ezetimibe/Simvastatin (Vytorin)

10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days

Intervention Type DRUG

Other Intervention Names

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Zocor Vytorin

Eligibility Criteria

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Inclusion Criteria

1. Male or female subjects aged 40 to 80 years
2. Documented stable atherosclerosis by angiography or vascular ultrasound (more that 20% luminal narrowing), peripheral arterial disease or type 2 diabetes mellitus (coronary heart disease (CHD) risk equivalent - Adult Treatment Program (ATP)-III guidelines)
3. LDL-cholesterol \>100mg/dL (indication to treat with statin)
4. Written informed consent
5. Primary care physician authorization letter to participate in the study.

Exclusion Criteria

1. Inability to give consent
2. Pre-menopausal women
3. Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
4. History of LFT \>2 times the upper normal limit
5. History of myopathy / myositis or CPK \> 10 times the upper normal limit
6. CPK above normal limits at study onset
7. Any evidence of inflammatory, infectious or neoplastic disease
8. History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.

Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No