Metabolic SyndromeNCT00485121
Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
A study testing Ezetimibe in people with Metabolic Syndrome and Obesity, run by Canadian Collaborative Research Network at 1 site in Canada.
Trial summary
The purpose of this study is to investigate the effects of adding ezetimibe to statin therapy on levels of inflammatory markers and adipokines in patients with atherosclerosis disease and features of the metabolic syndrome,whose LDL-c remains above target (> 2.0 mmol/L) despite statin monotherapy. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Metabolic Syndrome, Obesity, Coronary Artery Disease
- What is being tested?
- Ezetimibe
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2007to Apr 2009
- Phase
- Interventional
- 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
- Patients on statin therapy (no dose change within past 4 weeks) with LDL-c > 2mmol/l
- Presence of atherosclerosis (CHD* and/or cerebrovascular disease and/ or peripheral arterial disease (PAD)*) plus at least one of the following:
- Metabolic Syndrome (according to modified NCEP ATP III criteria, using waist circumference cut-offs of 80 cm for women and 90 cm for men in all subjects of Asian origin and cut-offs of 88 cm for women and 102 cm for men in all Caucasian subjects)
- Obesity (BMI > 30 Kg/m2 or waist circumference of > 102 for men and > 88 for women. For subjects of Asian origin the cutoff values should be 25, 90 and 80 respectively)
- CHD defined as (any one of the following): previous myocardial infarction; coronary angiography demonstrating at least 50% diameter stenosis in an epicardial coronary artery or its major branch; previous percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation (atherectomy included) or previous coronary artery bypass grafting (CABG)
- Cerebrovascular disease defined as (any one of the following): prior ischemic stroke, documented TIA, or flow-limiting stenosis in extracranial artery documented by Doppler or angiography.
- PAD defined as (any one of the following): prior peripheral arterial revascularization (PTA or surgery), amputation, or documented intermittent claudication with ABI < 0.9
Who cannot join
- Women who are pregnant, breast feeding, or not using a reliable method of contraception
- Clinical signs of congestive heart failure or measured left ventricular ejection fraction <40%
- Hemodynamically significant valvular heart disease or hypertrophic obstructive cardiomyopathy
- Renal dysfunction (creatinine > 1.8 x ULN)
- Hepatic disease (liver function test >1.5 x ULN [upper limit normal])
- Other significant laboratory abnormalities that the investigator feels may compromise the patient's safety by participation in the study
Show all 13Show fewer
- History of systemic inflammatory disease (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematous), myositis/myopathic process, or cancer)
- HIV
- Use of steroids or chemotherapy drugs within the past year or chronic use of nonsteroidal anti-inflammatory drugs besides aspirin (use for > 2 weeks within the past year);
- Known hypersensitivity to Ezetimibe
- Participation in another clinical study concurrently or within the 30-day phase prior to screening for entry into the present study
- Unwilling to provide written informed consent for study participant and/or
- Unreliability as a study participant as based on the investigator's prior knowledge of the patient, such as the inability or willingness to participate in or complete the study or the presence of concurrent physical or psychological disorders that may make it impractical for the patient to participate in or complete the study.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to investigate the effects of adding ezetimibe to statin therapy on levels of inflammatory markers and adipokines in patients with atherosclerosis disease and features of the metabolic syndrome,whose LDL-c remains above target (> 2.0 mmol/L) despite statin monotherapy.
We hypothesize that the addition of Ezetimibe (10mg per day for 12 weeks) to ongoing statin therapy in patients with atherosclerosis and features of the metabolic syndrome will favourably modify levels of inflammatory biomarkers and adipokines.
Read the detailed description
Atherosclerotic cardiovascular disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment and prevention. While there has been a trend over the last half century showing a general decline in the age-adjusted death rates of heart disease and stroke, the increasing epidemic of obesity, followed closely by insulin resistance and type 2 diabetes will likely slow the decline and promise to reverse this trend.
Obesity mediates increased cardiovascular disease risks through multiple pathways. Adipose tissue is no longer viewed as a passive repository for triacylglycerol storage and a source of free fatty acids (FFAs). It is recognized as a rich source of proinflammatory mediators, many of which are cytokines, growth factors and hormones that directly contribute to the proinflammatory milieu mediating vascular injury, insulin resistance and ultimately impacting on cardiovascular health. These proinflammatory adipocytokines, or adipokines include tumor necrosis factor- α (TNF α), interleukin-6 (IL-6), leptin, plasminogen activator inhibitor-1 (PAI-1), angiotensinogen, resistin and more recently C-reactive protein (CRP). On the other hand, nitric oxide (NO) and another adipokine called adiponectin confer protection against inflammation and obesity-linked insulin resistance.
The evolving role of augmented adipokine production in obese and insulin resistant states in cardiovascular disease risk opens new avenues for therapeutic interventions. Treatment of the metabolic syndrome will need to embrace new strategies to reduce the burden of proinflammatory adipokines. Lifestyle intervention remains the cornerstone therapy, but considerations should also be given to a number of drugs that can decrease the inflammatory adipokines.
Ezetimibe selectively inhibits the absorption of biliary and dietary cholesterol and phytosterols at the intestinal brush border. When added to or coadministered with a statin, ezetimibe produces significant incremental LDL-C, apolipoprotein (apo) B, and triglyceride (TG) reductions, beneficial effects on high-density lipoprotein cholesterol (HDL-C) compared to statin monotherapy, and is well tolerated with a low incidence of side effects.
It was previously demonstrated that in a 12 week trial that the addition of ezetimibe to simvastatin resulted in significant incremental reductions in CRP compared to simvastatin monotherapy.
The outlined study protocol investigates the effects of adding ezetimibe to statin therapy on levels of inflammatory markers and adipokines in patients with atherosclerosis and features of the metabolic syndrome, whose LDL-c remains above target (> 2.0 mmol/L) despite statin monotherapy.
- Conditions
- Metabolic Syndrome, Obesity, Coronary Artery Disease
- Being tested
- Ezetimibe
- Keywords
- Ezetimibe, Statin, Low- density lipoprotein cholesterol, Adipokine, Adiponectin, C-reactive protein, Coronary artery disease, Metabolic Syndrome, Obesity
- Medical subject headings
- Metabolic Syndrome, Obesity, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EzetimibeDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in adiponectin levels
Measured: 12 weeks
Secondary outcomes (1)
Change in CRP, PAI-1, Il-6, TNF-α, resistin, leptin levels and serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2007 (estimated)
- Study startApr 2007
- Primary completionMar 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic SyndromeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Canadian Collaborative Research Network
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough
- Investigators
- Milan K Gupta, MD, Principal investigator, Partners Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00485121
- Sponsor's protocol ID
- P05080
- Status last verified
- May 2008
- First submitted
- 8 Jun 2007
- Last updated
- 25 Nov 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
- ClinicalTrials.gov ID
- NCT00485121
- Acronym / sponsor ID
- P05080
- Conditions
- Metabolic Syndrome, Obesity, Coronary Artery Disease
- Keywords
- Ezetimibe, Statin, Low- density lipoprotein cholesterol, Adipokine, Adiponectin, C-reactive protein, Coronary artery disease, Metabolic Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Canadian Collaborative Research NetworkUniversity, hospital or other
- Collaborators
- Schering-Plough
- Study start
- Apr 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 12 Jun 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.
The purpose of this study is to investigate the effects of adding ezetimibe to statin therapy on levels of inflammatory markers and adipokines in patients with atherosclerosis disease and features of the metabolic syndrome,whose LDL-c remains above target (> 2.0 mmol/L) despite statin monotherapy.
We hypothesize that the addition of Ezetimibe (10mg per day for 12 weeks) to ongoing statin therapy in patients with atherosclerosis and features of the metabolic syndrome will favourably modify levels of inflammatory biomarkers and adipokines.
Detailed description
Atherosclerotic cardiovascular disease remains the leading cause of death in industrialized nations despite major advances in its diagnosis, treatment and prevention. While there has been a trend over the last half century showing a general decline in the age-adjusted death rates of heart disease and stroke, the increasing epidemic of obesity, followed closely by insulin resistance and type 2 diabetes will likely slow the decline and promise to reverse this trend.
Obesity mediates increased cardiovascular disease risks through multiple pathways. Adipose tissue is no longer viewed as a passive repository for triacylglycerol storage and a source of free fatty acids (FFAs). It is recognized as a rich source of proinflammatory mediators, many of which are cytokines, growth factors and hormones that directly contribute to the proinflammatory milieu mediating vascular injury, insulin resistance and ultimately impacting on cardiovascular health. These proinflammatory adipocytokines, or adipokines include tumor necrosis factor- α (TNF α), interleukin-6 (IL-6), leptin, plasminogen activator inhibitor-1 (PAI-1), angiotensinogen, resistin and more recently C-reactive protein (CRP). On the other hand, nitric oxide (NO) and another adipokine called adiponectin confer protection against inflammation and obesity-linked insulin resistance.
The evolving role of augmented adipokine production in obese and insulin resistant states in cardiovascular disease risk opens new avenues for therapeutic interventions. Treatment of the metabolic syndrome will need to embrace new strategies to reduce the burden of proinflammatory adipokines. Lifestyle intervention remains the cornerstone therapy, but considerations should also be given to a number of drugs that can decrease the inflammatory adipokines.
Ezetimibe selectively inhibits the absorption of biliary and dietary cholesterol and phytosterols at the intestinal brush border. When added to or coadministered with a statin, ezetimibe produces significant incremental LDL-C, apolipoprotein (apo) B, and triglyceride (TG) reductions, beneficial effects on high-density lipoprotein cholesterol (HDL-C) compared to statin monotherapy, and is well tolerated with a low incidence of side effects.
It was previously demonstrated that in a 12 week trial that the addition of ezetimibe to simvastatin resulted in significant incremental reductions in CRP compared to simvastatin monotherapy.
The outlined study protocol investigates the effects of adding ezetimibe to statin therapy on levels of inflammatory markers and adipokines in patients with atherosclerosis and features of the metabolic syndrome, whose LDL-c remains above target (> 2.0 mmol/L) despite statin monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients on statin therapy (no dose change within past 4 weeks) with LDL-c > 2mmol/l
- Presence of atherosclerosis (CHD* and/or cerebrovascular disease and/ or peripheral arterial disease (PAD)*) plus at least one of the following:
Key exclusion criteria (13 listed)
- Women who are pregnant, breast feeding, or not using a reliable method of contraception
- Clinical signs of congestive heart failure or measured left ventricular ejection fraction <40%
- Hemodynamically significant valvular heart disease or hypertrophic obstructive cardiomyopathy
- Renal dysfunction (creatinine > 1.8 x ULN)
- Hepatic disease (liver function test >1.5 x ULN [upper limit normal])
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 |
|---|---|---|
| Ezetimibe | Drug | – |
Primary outcome
Change in adiponectin levels
Time frame: 12 weeks
1 secondary outcome
Change in CRP, PAI-1, Il-6, TNF-α, resistin, leptin levels and serum lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol, Triglycerides).
Time frame: 12 weeks
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 25 Nov 2010.
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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.
Milan K Gupta, MD principal investigator
Partners Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ezetimibe in people with Metabolic Syndrome and Obesity, run by Canadian Collaborative Research Network at 1 site in Canada.
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 7 inclusion and 13 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 25 Nov 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 Canada. 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.
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?
Change in adiponectin levels (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2010.