Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
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|ClinicalTrials.gov Identifier: NCT00485121|
Recruitment Status : Completed
First Posted : June 12, 2007
Last Update Posted : November 25, 2010
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 or disease||Intervention/treatment||Phase|
|Metabolic Syndrome Obesity Coronary Artery Disease||Drug: Ezetimibe||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis|
|Study Start Date :||April 2007|
|Actual Primary Completion Date :||March 2009|
|Actual Study Completion Date :||April 2009|
U.S. FDA Resources
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00485121
|Brampton, Ontario, Canada, L6V 1B4|
|Principal Investigator:||Milan K Gupta, MD||Partners Research|