Ignite Creation Date:
2024-05-06 @ 3:08 AM
Last Modification Date:
2024-10-26 @ 11:29 AM
Study NCT ID:
NCT02219906
Status:
COMPLETED
Last Update Posted:
2019-04-19
First Post:
2014-08-14
Brief Title:
Resveratrol in Metabolic Syndrome Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Sponsor:
Vanderbilt University
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Resveratrol in Metabolic Syndrome Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Status:
COMPLETED
Status Verified Date:
2019-04
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:
Metabolic syndrome is a group of risk factors that increase a patients likelihood for heart attack stroke and diabetes Our research is aimed at understanding whether a drug resveratrol commonly found in grapes and red wine would have any benefit in reducing risk factors in patients that have metabolic syndrome Despite the use of aspirin and cholesterol reducing medications patients with metabolic syndrome still often have sticky platelets and dysfunctional lipid profile This is likely due to inflammation and high oxidative state In animal studies this drug has reduced platelet stickiness and reduced oxidative stress However the effects of this drug have not been researched in patients with metabolic syndrome
We are interested in studying whether the benefits of resveratrol described in animal models can be translated to patients with metabolic syndrome who display high markers of oxidative stress We plan to give a short intervention of drug to patients and then determine if the drug successfully
1 Decreases the stickiness of platelets This is important because sticky platelets are more likely to form clot and contribute to plaque formation
2 Reduce the circulating dysfunctional HDL HDL and its protein and lipid constituents help to inhibit oxidation inflammation activation of the blood vessel wall coagulation and platelet aggregation Dysfunctional HDL as occurs in metabolic syndrome patients cannot properly protect against atherosclerosis
We are interested in studying whether the benefits of resveratrol described in animal models can be translated to patients with metabolic syndrome who display high markers of oxidative stress We plan to give a short intervention of drug to patients and then determine if the drug successfully
1 Decreases the stickiness of platelets This is important because sticky platelets are more likely to form clot and contribute to plaque formation
2 Reduce the circulating dysfunctional HDL HDL and its protein and lipid constituents help to inhibit oxidation inflammation activation of the blood vessel wall coagulation and platelet aggregation Dysfunctional HDL as occurs in metabolic syndrome patients cannot properly protect against atherosclerosis
Detailed Description:
Patients with metabolic syndrome are at increased risk of thrombotic complications including myocardial infarction and cardiovascular death A meta-analysis of the studies assessing cardiovascular risk in metabolic syndrome found a pooled relative risk for incident cardiovascular events and death of 178 This propensity for thrombotic vascular events is in the context of an increasing prevalence of metabolic syndrome which in the 2003-2006 NHANES Survey was found in 34 of the US population over the age of 20
Two important contributors to the development of myocardial infarction and stroke are lipid rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring of these plaques A growing body of evidence implicates oxidative modification of lipoprotein lipids and apolipoproteins in the genesis of plaques Platelet hyperactivity and the variable response to antiplatelet therapy are features of the metabolic syndrome Oxidative modifications of LDL enhance activation of platelets which themselves are oxidatively stressed Myeloperoxidase MPO initiates lipid peroxidation leading to dysfunctional HDL production Therefore the hypotheses for the proposed investigations will address the effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients with metabolic syndrome Resveratrol as predicted from its structure is an electron rich molecule that can reduce free radicals It has distinctive actions however that differ from compounds that are conventionally referred to as anti-oxidants It has particular potency as an inhibitor of radical formation by a number of peroxidases that likely participate in the pathophysiology of metabolic syndrome These include MPO the peroxidase site of prostaglandin H synthase-1 PGHS-1 cyclooxygenase-1COX-1 and cytochrome c
We will test the hypothesis that
1 resveratrol reduces platelet activation in patients with metabolic syndrome and
2 that resveratrol reduces the oxidative modification of HDL proteins in patients with metabolic syndrome
Two important contributors to the development of myocardial infarction and stroke are lipid rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring of these plaques A growing body of evidence implicates oxidative modification of lipoprotein lipids and apolipoproteins in the genesis of plaques Platelet hyperactivity and the variable response to antiplatelet therapy are features of the metabolic syndrome Oxidative modifications of LDL enhance activation of platelets which themselves are oxidatively stressed Myeloperoxidase MPO initiates lipid peroxidation leading to dysfunctional HDL production Therefore the hypotheses for the proposed investigations will address the effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients with metabolic syndrome Resveratrol as predicted from its structure is an electron rich molecule that can reduce free radicals It has distinctive actions however that differ from compounds that are conventionally referred to as anti-oxidants It has particular potency as an inhibitor of radical formation by a number of peroxidases that likely participate in the pathophysiology of metabolic syndrome These include MPO the peroxidase site of prostaglandin H synthase-1 PGHS-1 cyclooxygenase-1COX-1 and cytochrome c
We will test the hypothesis that
1 resveratrol reduces platelet activation in patients with metabolic syndrome and
2 that resveratrol reduces the oxidative modification of HDL proteins in patients with metabolic syndrome
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