<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02219906</url>
  </required_header>
  <id_info>
    <org_study_id>130996</org_study_id>
    <nct_id>NCT02219906</nct_id>
  </id_info>
  <brief_title>Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation</brief_title>
  <official_title>Resveratrol in Metabolic Syndrome: Effect on Platelet Hyper-reactivity and HDL Lipid Peroxidation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Metabolic syndrome is a group of risk factors that increase a patient's likelihood for heart&#xD;
      attack, stroke and diabetes. Our research is aimed at understanding whether a drug,&#xD;
      resveratrol, commonly found in grapes and red wine, would have any benefit in reducing risk&#xD;
      factors in patients that have metabolic syndrome. Despite the use of aspirin and cholesterol&#xD;
      reducing medications, patients with metabolic syndrome still often have sticky platelets and&#xD;
      dysfunctional lipid profile. This is likely due to inflammation and high oxidative state. In&#xD;
      animal studies, this drug has reduced platelet stickiness and reduced oxidative stress.&#xD;
      However, the effects of this drug have not been researched in patients with metabolic&#xD;
      syndrome.&#xD;
&#xD;
      We are interested in studying whether the benefits of resveratrol described in animal models&#xD;
      can be translated to patients with metabolic syndrome who display high markers of oxidative&#xD;
      stress. We plan to give a short intervention of drug to patients and then determine if the&#xD;
      drug successfully:&#xD;
&#xD;
        1. Decreases the stickiness of platelets. This is important because sticky platelets are&#xD;
           more likely to form clot and contribute to plaque formation.&#xD;
&#xD;
        2. Reduce the circulating dysfunctional HDL. HDL and its protein and lipid constituents&#xD;
           help to inhibit oxidation, inflammation, activation of the blood vessel wall,&#xD;
           coagulation, and platelet aggregation. Dysfunctional HDL, as occurs in metabolic&#xD;
           syndrome patients, cannot properly protect against atherosclerosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with metabolic syndrome are at increased risk of thrombotic complications, including&#xD;
      myocardial infarction and cardiovascular death. A meta-analysis of the studies assessing&#xD;
      cardiovascular risk in metabolic syndrome found a pooled relative risk for incident&#xD;
      cardiovascular events and death of 1.78. This propensity for thrombotic vascular events is in&#xD;
      the context of an increasing prevalence of metabolic syndrome, which in the 2003-2006 NHANES&#xD;
      Survey was found in 34% of the US population over the age of 20.&#xD;
&#xD;
      Two important contributors to the development of myocardial infarction and stroke are lipid&#xD;
      rich atheromatous plaques and concomitant platelet aggregation in response to the fissuring&#xD;
      of these plaques. A growing body of evidence implicates oxidative modification of lipoprotein&#xD;
      lipids and apolipoproteins in the genesis of plaques. Platelet hyperactivity and the variable&#xD;
      response to antiplatelet therapy are features of the metabolic syndrome. Oxidative&#xD;
      modifications of LDL enhance activation of platelets, which themselves are oxidatively&#xD;
      stressed. Myeloperoxidase (MPO) initiates lipid peroxidation leading to dysfunctional HDL&#xD;
      production. Therefore, the hypotheses for the proposed investigations will address the&#xD;
      effects of resveratrol on platelet hyperactivity and HDL protein modifications in patients&#xD;
      with metabolic syndrome. Resveratrol, as predicted from its structure, is an electron rich&#xD;
      molecule that can reduce free radicals. It has distinctive actions, however, that differ from&#xD;
      compounds that are conventionally referred to as &quot;anti-oxidants&quot;. It has particular potency&#xD;
      as an inhibitor of radical formation by a number of peroxidases that likely participate in&#xD;
      the pathophysiology of metabolic syndrome. These include MPO, the peroxidase site of&#xD;
      prostaglandin H synthase-1 (PGHS-1; cyclooxygenase-1(COX-1)) and cytochrome c.&#xD;
&#xD;
      We will test the hypothesis that:&#xD;
&#xD;
        1. resveratrol reduces platelet activation in patients with metabolic syndrome. and&#xD;
&#xD;
        2. that resveratrol reduces the oxidative modification of HDL proteins in patients with&#xD;
           metabolic syndrome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">April 7, 2019</completion_date>
  <primary_completion_date type="Actual">February 7, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in parameters of platelet activation</measure>
    <time_frame>baseline, 3 weeks after intervention</time_frame>
    <description>Measure platelet-monocyte aggregates by flow cytometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in parameter for platelet oxidative stress</measure>
    <time_frame>Baseline, 3 weeks after intervention</time_frame>
    <description>Measure malondialdehyde adducts of platelet proteins</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in parameter for platelet oxidation levels</measure>
    <time_frame>Baseline, 3 week after intervention</time_frame>
    <description>Measure superoxide production by platelets</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum Thromboxane measurments</measure>
    <time_frame>Baseline, 3 weeks after intervention</time_frame>
    <description>Measure thromboxane to assess inflammation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in oxidative modifications of HDL</measure>
    <time_frame>baseline, three weeks after intervention</time_frame>
    <description>Measure change in malondialdehyde adducts in HDL proteins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasma oxidative stress</measure>
    <time_frame>baselines, three weeks after intervention</time_frame>
    <description>Measure change in plasma isoprostanes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo capsule given three times daily X 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Resveratrol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Resveratrol 1 gram three times daily X 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Resveratrol</intervention_name>
    <description>1000mg tid</description>
    <arm_group_label>Resveratrol</arm_group_label>
    <other_name>tid dosing</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1000mg tid placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>tid dosing</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Metabolic Syndrome&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Evidence of coronary artery disease&#xD;
&#xD;
          -  Indication for use of aspirin for secondary prevention of thrombotic events&#xD;
&#xD;
          -  Use of non-steroidal anti-inflammatory drugs or anti-platelet agents&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients with history of bleeding or gastrointestinal ulcers&#xD;
&#xD;
          -  Patients with major illnesses such as ongoing malignancies, infections, cirrhosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John A Oates, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77004</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>April 17, 2019</last_update_submitted>
  <last_update_submitted_qc>April 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 19, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>John Oates</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Resveratrol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02219906
org study id: 130996
nct id: NCT02219906
lead sponsor: 
has dmc: Yes
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Change in parameters of platelet activation
time frame: baseline, 3 weeks after intervention
description: Measure platelet-monocyte aggregates by flow cytometry
measure: Change in parameter for platelet oxidative stress
time frame: Baseline, 3 weeks after intervention
description: Measure malondialdehyde adducts of platelet proteins
measure: Change in parameter for platelet oxidation levels
time frame: Baseline, 3 week after intervention
description: Measure superoxide production by platelets
measure: Serum Thromboxane measurments
time frame: Baseline, 3 weeks after intervention
description: Measure thromboxane to assess inflammation
measure: Change in oxidative modifications of HDL
time frame: baseline, three weeks after intervention
description: Measure change in malondialdehyde adducts in HDL proteins
measure: Change in plasma oxidative stress
time frame: baselines, three weeks after intervention
description: Measure change in plasma isoprostanes
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo capsule given three times daily X 3 weeks
arm group label: Resveratrol
arm group type: Experimental
description: Resveratrol 1 gram three times daily X 3 weeks
intervention type: Dietary Supplement
intervention name: Resveratrol
description: 1000mg tid
arm group label: Resveratrol
other name: tid dosing
intervention type: Dietary Supplement
intervention name: Placebo
description: 1000mg tid placebo
arm group label: Placebo
other name: tid dosing
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: John A Oates, MD
role: Principal Investigator
affiliation: Vanderbilt University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: John Oates
investigator title: Professor of Medicine
mesh term: Metabolic Syndrome
mesh term: Syndrome
mesh term: Resveratrol
sharing ipd: No