Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis
Rho-kinase in Patients With Atherosclerosis: Effects of Statins A Randomized Clinical Trial Comparing Ezetimibe/Simvastatin and Simvastatin
1 other identifier
interventional
40
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_4
Started Sep 2007
Shorter than P25 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2007
CompletedFirst Submitted
Initial submission to the registry
November 16, 2007
CompletedFirst Posted
Study publicly available on registry
November 19, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2008
CompletedFebruary 24, 2010
February 1, 2010
4 months
November 16, 2007
February 23, 2010
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
changes in the lipid profile change and Rho-kinase expression and activity
28 days
Secondary Outcomes (1)
correlation between changes in Rho-kinase expression and activity with the changes in LDL-C, hsCRP and BAFMD
28 days
Study Arms (2)
high dose statin
EXPERIMENTAL40mg of Simvastatin (n=20)
combination arm
ACTIVE COMPARATOR10mg/10mg of Ezetimibe/Simvastatin (n=20)
Interventions
40mg of Simvastatin (n=20) orally per-day for 28 days
10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days
Eligibility Criteria
You may qualify if:
- Male or female subjects aged 40 to 80 years
- 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)
- LDL-cholesterol \>100mg/dL (indication to treat with statin)
- Written informed consent
- Primary care physician authorization letter to participate in the study.
You may not qualify if:
- Inability to give consent
- Pre-menopausal women
- Current use of antibiotics, anti-inflammatory or immunosuppressant drugs
- History of LFT \>2 times the upper normal limit
- History of myopathy / myositis or CPK \> 10 times the upper normal limit
- CPK above normal limits at study onset
- Any evidence of inflammatory, infectious or neoplastic disease
- History of CABG, PCI or acute ischemic syndrome in the preceding 3 months.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Cheng Kung University Hospital
Tainan, 704, Taiwan
Related Publications (1)
Liu PY, Liu YW, Lin LJ, Chen JH, Liao JK. Evidence for statin pleiotropy in humans: differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity, endothelial function, and inflammation. Circulation. 2009 Jan 6;119(1):131-8. doi: 10.1161/CIRCULATIONAHA.108.813311. Epub 2008 Dec 15.
PMID: 19075102DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jyh-Hong Chen, MD, PhD
National Cheng-Kung University Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
Study Record Dates
First Submitted
November 16, 2007
First Posted
November 19, 2007
Study Start
September 1, 2007
Primary Completion
January 1, 2008
Study Completion
February 1, 2008
Last Updated
February 24, 2010
Record last verified: 2010-02