Ignite Creation Date:
2024-05-05 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00485121
Status:
COMPLETED
Last Update Posted:
2010-11-25
First Post:
2007-06-08
Brief Title:
Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
Sponsor:
Canadian Collaborative Research Network
Organization:
Canadian Collaborative Research Network
Study Overview
Official Title:
Effects of Ezetimibe Add-On to Statin Therapy on Adipokine Production in Obese and Metabolic Syndrome Patients With Atherosclerosis
Status:
COMPLETED
Status Verified Date:
2008-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 syndromewhose LDL-c remains above target 20 mmolL 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
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 20 mmolL despite statin monotherapy
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 20 mmolL despite statin monotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None