An interventional study of Ezetimibe in Metabolic Syndrome, Obesity and Coronary Artery Disease, sponsored by Canadian Collaborative Research Network. Completed at 1 site in Canada. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2010-11-25.
Sponsored by Canadian Collaborative Research Network · Not applicable, Interventional, and Treatment
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.
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.
5,598 studies on the registry are indexed under Coronary Artery Disease; 957 are open to participants now.
This study's planned enrollment of 50 is below the median of 124 across 3,436 interventional studies indexed under Coronary Artery Disease.
Browse Coronary Artery Disease studies →Canadian Collaborative Research Network is the lead sponsor of 5 studies on the registry; none are open to participants now.
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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:
Change in adiponectin levels
Time frame: 12 weeks
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
This study is completed, as verified in May 2008. You cannot join it, but the record below documents what was studied.
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Canadian Collaborative Research Network