AtherosclerosisPhase 4NCT00560170
Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis
A Phase 4 study testing Simvastatin (Zocor) and 10mg/10mg of Ezetimibe/Simvastatin (Vytorin) in people with Atherosclerosis, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- Simvastatin (Zocor) and 10mg/10mg of Ezetimibe/Simvastatin (Vytorin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteTaiwan
- Study dates
- Sep 2007to Feb 2008
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Rho-kinase in Patients With Atherosclerosis: Effects of Statins A Randomized Clinical Trial Comparing Ezetimibe/Simvastatin and Simvastatin
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.
Read the 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.
- Conditions
- Atherosclerosis
- Being tested
- Simvastatin (Zocor), 10mg/10mg of Ezetimibe/Simvastatin (Vytorin)
- Keywords
- HMG-CoA Reductase Inhibitors, endothelial function, HMG-CoA Reductase Inhibitors on vascular protection
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin (Zocor)Drug
Also called Zocor
40mg of Simvastatin (n=20) orally per-day for 28 days
10mg/10mg of Ezetimibe/Simvastatin (Vytorin)Drug
Also called Vytorin
10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days
| Study group | Role | What they receive |
|---|---|---|
| high dose statin | Experimental | 40mg of Simvastatin (n=20) Receives: Drug: Simvastatin (Zocor) |
| combination arm | Active comparator | 10mg/10mg of Ezetimibe/Simvastatin (n=20) Receives: Drug: 10mg/10mg of Ezetimibe/Simvastatin (Vytorin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
changes in the lipid profile change and Rho-kinase expression and activity
Measured: 28 days
Secondary outcomes (1)
correlation between changes in Rho-kinase expression and activity with the changes in LDL-C, hsCRP and BAFMD
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2007 (estimated)
- Study startSep 2007
- Primary completionJan 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Jyh-Hong Chen, MD, PhD, Principal investigator, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00560170
- Sponsor's protocol ID
- NCKUH-01/HR-95-112
- Status last verified
- Feb 2010
- First submitted
- 16 Nov 2007
- Last updated
- 24 Feb 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19075102
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rho-kinase in Patients With Atherosclerosis: Effects of Statins A Randomized Clinical Trial Comparing Ezetimibe/Simvastatin and Simvastatin
- ClinicalTrials.gov ID
- NCT00560170
- Acronym / sponsor ID
- NCKUH-01/HR-95-112
- Conditions
- Atherosclerosis
- Keywords
- HMG-CoA Reductase Inhibitors, endothelial function, HMG-CoA Reductase Inhibitors on vascular protection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- Sep 2007
- Primary completion
- Jan 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 19 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| high dose statin | Experimental | Drug: Simvastatin (Zocor)40mg of Simvastatin (n=20) |
| combination arm | Active comparator | Drug: 10mg/10mg of Ezetimibe/Simvastatin (Vytorin)10mg/10mg of Ezetimibe/Simvastatin (n=20) |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
Key exclusion criteria (8 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Simvastatin (Zocor)Also: Zocor40mg of Simvastatin (n=20) orally per-day for 28 days | Drug | high dose statin |
| 10mg/10mg of Ezetimibe/Simvastatin (Vytorin)Also: Vytorin10mg/10mg of Ezetimibe/Simvastatin (n=20) orally per-day for 28 days | Drug | combination arm |
Primary outcome
changes in the lipid profile change and Rho-kinase expression and activity
Time frame: 28 days
1 secondary outcome
correlation between changes in Rho-kinase expression and activity with the changes in LDL-C, hsCRP and BAFMD
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2010.
- Derived from this study: PubMed 19075102Liu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jyh-Hong Chen, MD, PhD principal investigator
National Cheng-Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin (Zocor) and 10mg/10mg of Ezetimibe/Simvastatin (Vytorin) in people with Atherosclerosis, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
changes in the lipid profile change and Rho-kinase expression and activity (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00560170, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2010.