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Sponsors and Collaborators: |
Canadian Cardiovascular Research Network Schering-Plough |
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Information provided by: | Canadian Cardiovascular Research Network |
ClinicalTrials.gov Identifier: | NCT00485121 |
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.
Condition | Intervention |
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Metabolic Syndrome Obesity Coronary Artery Disease |
Drug: Ezetimibe |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study |
Official Title: | Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis |
Estimated Enrollment: | 50 |
Study Start Date: | April 2007 |
Estimated Study Completion Date: | October 2008 |
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.
Ages Eligible for Study: | 40 Years to 80 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Presence of atherosclerosis (CHD* and/or cerebrovascular disease** and/ or peripheral arterial disease (PAD)***) plus at least one of the following:
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.
Exclusion Criteria:
Contact: Milan K Gupta, MD | 905- 452- 6213 | mkgupta@rogers.com |
Canada, Ontario | |
Partners Research | Recruiting |
Brampton, Ontario, Canada, L6V 1B4 | |
Principal Investigator: Milan K Gupta, MD |
Principal Investigator: | Milan K Gupta, MD | Partners Research |
Study ID Numbers: | P05080 |
Study First Received: | June 8, 2007 |
Last Updated: | May 26, 2008 |
ClinicalTrials.gov Identifier: | NCT00485121 History of Changes |
Health Authority: | Canada: Health Canada |
Ezetimibe Statin Low- density lipoprotein cholesterol Adipokine Adiponectin |
C-reactive protein Coronary artery disease Metabolic Syndrome Obesity |
Antimetabolites Atherosclerosis Arterial Occlusive Diseases Obesity Heart Diseases Antilipemic Agents Myocardial Ischemia Vascular Diseases Ezetimibe Overweight |
Anticholesteremic Agents Arteriosclerosis Ischemia Hydroxymethylglutaryl-CoA Reductase Inhibitors Body Weight Coronary Disease Signs and Symptoms Nutrition Disorders Overnutrition Coronary Artery Disease |
Atherosclerosis Antimetabolites Molecular Mechanisms of Pharmacological Action Myocardial Ischemia Overweight Ezetimibe Arteriosclerosis Body Weight Signs and Symptoms Pathologic Processes Syndrome Therapeutic Uses Nutrition Disorders |
Cardiovascular Diseases Arterial Occlusive Diseases Obesity Heart Diseases Disease Antilipemic Agents Vascular Diseases Anticholesteremic Agents Pharmacologic Actions Coronary Disease Overnutrition Coronary Artery Disease |