Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis - Full Text View

Sponsor:	National Cheng-Kung University Hospital
Information provided by:	National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier:	NCT00560170

Purpose

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.

Condition	Intervention	Phase
Atherosclerosis	Drug: Simvastatin (Zocor) Drug: 10mg/10mg of Ezetimibe/Simvastatin (Vytorin)	Phase IV

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	Rho-Kinase in Patients With Atherosclerosis: Effects of Statins A Randomized Clinical Trial Comparing Ezetimibe/Simvastatin and Simvastatin

Resource links provided by NLM:

MedlinePlus related topics: Statins

Drug Information available for: Simvastatin Ezetimibe Vytorin

U.S. FDA Resources

Further study details as provided by National Cheng-Kung University Hospital:

Primary Outcome Measures:

changes in the lipid profile change and Rho-kinase expression and activity [ Time Frame: 28 days ]

Secondary Outcome Measures:

correlation between changes in Rho-kinase expression and activity with the changes in LDL-C, hsCRP and BAFMD [ Time Frame: 28 days ]

Estimated Enrollment:	40
Study Start Date:	September 2007
Estimated Study Completion Date:	February 2008

Arms	Assigned Interventions
1: Experimental 40mg of Simvastatin (n=20)	Drug: Simvastatin (Zocor) 40mg of Simvastatin (n=20) orally per-day for 28 days
2: Active Comparator 10mg/10mg of Ezetimibe/Simvastatin (n=20)	Drug: 10mg/10mg of Ezetimibe/Simvastatin (Vytorin) 10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days

Detailed Description:

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:

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.

Exclusion criteria:

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.

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00560170

Contacts

Contact: Jyh-Hong Chen, MD, PhD	886-6-2353535 ext 2389	jyhhong@mail.ncku.edu.tw
Contact: Ping-Yen Liu, MD, PhD	886-6-2353535 ext 2389	larry@mail.ncku.edu.tw

Locations

Taiwan
National Cheng Kung University Hospital	Recruiting
Tainan, Taiwan, 704
Contact: Jyh-Hong Chen, MD, PhD 886-6-2353535 ext 2389 jyhhong@mail.ncku.edu.tw
Contact: Ping-Yen Liu, MD, PhD 886-6-2353535 ext 2389 larry@mail.ncku.edu.tw
Principal Investigator: Jyh-Hong Chen, MD, PhD
Sub-Investigator: Ping-Yen Liu, MD, PhD
Sub-Investigator: Yen-Wen Liu, MD
Sub-Investigator: Li-Jen Lin, MD

Sponsors and Collaborators

National Cheng-Kung University Hospital

Investigators

Principal Investigator:

Jyh-Hong Chen, MD, PhD

National Cheng-Kung University Hospital

More Information

No publications provided by National Cheng-Kung University Hospital

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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. Epub 2008 Dec 15.

Study ID Numbers:	NCKUH-01/HR-95-112
Study First Received:	November 16, 2007
Last Updated:	November 16, 2007
ClinicalTrials.gov Identifier:	NCT00560170 History of Changes
Health Authority:	Taiwan: Institutional Review Board

Keywords provided by National Cheng-Kung University Hospital:

HMG-CoA Reductase Inhibitors
endothelial function
HMG-CoA Reductase Inhibitors on vascular protection

Additional relevant MeSH terms:

Atherosclerosis
Arterial Occlusive Diseases
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Simvastatin
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors

Ezetimibe
Anticholesteremic Agents
Arteriosclerosis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Therapeutic Uses
Cardiovascular Diseases

ClinicalTrials.gov processed this record on February 08, 2010