Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis

This study has been completed.
Sponsor:
Information provided by:
National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier:
NCT00560170
First received: November 16, 2007
Last updated: February 23, 2010
Last verified: February 2010
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
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:


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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: September 2007
Study Completion Date: February 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: high dose statin
40mg of Simvastatin (n=20)
Drug: Simvastatin (Zocor)
40mg of Simvastatin (n=20) orally per-day for 28 days
Other Name: Zocor
Active Comparator: combination arm
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
Other Name: Vytorin

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:

  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.
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan, 704
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 ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ASSISTANT PROFESSOR, National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier: NCT00560170     History of Changes
Other Study ID Numbers: NCKUH-01/HR-95-112
Study First Received: November 16, 2007
Last Updated: February 23, 2010
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
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Simvastatin
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014