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Trial record 73 of 87 for:    ASPIRIN AND thromboxane

Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation

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ClinicalTrials.gov Identifier: NCT02219906
Recruitment Status : Completed
First Posted : August 19, 2014
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
John Oates, Vanderbilt University

Brief Summary:

Metabolic syndrome is a group of risk factors that increase a patient's 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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Dietary Supplement: Resveratrol Dietary Supplement: Placebo Not Applicable

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 1.78. 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-1(COX-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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation
Study Start Date : May 2014
Actual Primary Completion Date : February 7, 2019
Actual Study Completion Date : April 7, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Resveratrol

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo capsule given three times daily X 3 weeks
Dietary Supplement: Placebo
1000mg tid placebo
Other Name: tid dosing

Experimental: Resveratrol
Resveratrol 1 gram three times daily X 3 weeks
Dietary Supplement: Resveratrol
1000mg tid
Other Name: tid dosing




Primary Outcome Measures :
  1. Change in parameters of platelet activation [ Time Frame: baseline, 3 weeks after intervention ]
    Measure platelet-monocyte aggregates by flow cytometry

  2. Change in parameter for platelet oxidative stress [ Time Frame: Baseline, 3 weeks after intervention ]
    Measure malondialdehyde adducts of platelet proteins

  3. Change in parameter for platelet oxidation levels [ Time Frame: Baseline, 3 week after intervention ]
    Measure superoxide production by platelets

  4. Serum Thromboxane measurments [ Time Frame: Baseline, 3 weeks after intervention ]
    Measure thromboxane to assess inflammation


Secondary Outcome Measures :
  1. Change in oxidative modifications of HDL [ Time Frame: baseline, three weeks after intervention ]
    Measure change in malondialdehyde adducts in HDL proteins

  2. Change in plasma oxidative stress [ Time Frame: baselines, three weeks after intervention ]
    Measure change in plasma isoprostanes



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Ages Eligible for Study:   30 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metabolic Syndrome

Exclusion Criteria:

  • Evidence of coronary artery disease
  • Indication for use of aspirin for secondary prevention of thrombotic events
  • Use of non-steroidal anti-inflammatory drugs or anti-platelet agents
  • Pregnancy
  • Patients with history of bleeding or gastrointestinal ulcers
  • Patients with major illnesses such as ongoing malignancies, infections, cirrhosis

Information from the National Library of Medicine

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): NCT02219906


Locations
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United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor University
Houston, Texas, United States, 77004
Sponsors and Collaborators
Vanderbilt University
Investigators
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Principal Investigator: John A Oates, MD Vanderbilt University

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Responsible Party: John Oates, Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT02219906     History of Changes
Other Study ID Numbers: 130996
First Posted: August 19, 2014    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Metabolic Syndrome
Syndrome
Disease
Pathologic Processes
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Resveratrol
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Antimutagenic Agents
Anticarcinogenic Agents