<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/NCT01714102</url>
  </required_header>
  <id_info>
    <org_study_id>JWA-0786</org_study_id>
    <nct_id>NCT01714102</nct_id>
  </id_info>
  <brief_title>Resveratrol and the Metabolic Syndrome</brief_title>
  <official_title>The Effects of Trans-Resveratrol (RSV) on Insulin Resistance, Inflammation, and the Metabolic Syndrome: A Placebo Controlled, Double-Blind Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rockefeller University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rockefeller University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Metabolic syndrome is a serious health condition that affects about 35 percent of adults and&#xD;
      places them at higher risk of cardiovascular disease, diabetes, stroke and diseases related&#xD;
      to fatty buildups in artery walls. The underlying causes of metabolic syndrome are obesity,&#xD;
      being overweight, physical inactivity and genetic factors. In recent decades, the prevalence&#xD;
      has increased dramatically in the United States. Lifestyle interventions including dietary&#xD;
      modification, physical activity and weight loss form the basis of treatment for these&#xD;
      patients. However, research has shown that even when people are able to incorporate these&#xD;
      changes, they often revert back to their usual lifestyle resulting in weight gain and&#xD;
      continued risk for diabetes and heart disease.&#xD;
&#xD;
      Resveratrol, a natural plant derived compound found in grapes, peanuts and red wine, has been&#xD;
      found to reverse some of the features of the metabolic syndrome (insulin resistance, high&#xD;
      triglycerides, high blood pressure) in rodents. These improvements occurred without weight&#xD;
      loss, and were proven to be a direct result of resveratrol ingestion. Other studies reveal&#xD;
      improvement in cardiovascular health, tumor suppression, and longevity. However, there are&#xD;
      few studies investigating these beneficial effects in humans. Investigators propose to prove&#xD;
      that resveratrol, administered to subjects with the metabolic syndrome, under controlled&#xD;
      conditions of weight stability, common diet, and strict compliance with the study drug, will&#xD;
      improve the symptoms of the metabolic syndrome, thereby decreasing the chance of developing&#xD;
      diabetes or heart disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The metabolic syndrome is a serious health condition that affects about 35 percent of adults&#xD;
      and places them at higher risk of cardiovascular disease, diabetes, stroke and diseases&#xD;
      related to fatty buildups in artery walls. The underlying causes of metabolic syndrome are&#xD;
      obesity, being overweight, physical inactivity and genetic factors. In recent decades, the&#xD;
      prevalence has increased dramatically in the United States. Lifestyle interventions including&#xD;
      dietary modification, physical activity and weight loss form the basis of treatment for these&#xD;
      patients. However, research has shown that even when people are able to incorporate these&#xD;
      changes, they often revert back to their usual lifestyle resulting in weight gain and&#xD;
      continued risk for diabetes and heart disease.&#xD;
&#xD;
      Resveratrol, a natural plant derived compound found in grapes, peanuts and red wine, has been&#xD;
      found to reverse some of the features of the metabolic syndrome (insulin resistance, high&#xD;
      triglycerides, high blood pressure) in rodents. These improvements occurred without weight&#xD;
      loss, and were proven to be a direct result of resveratrol ingestion. Other studies reveal&#xD;
      improvement in cardiovascular health, tumor suppression, and longevity. However, there are&#xD;
      few studies investigating these beneficial effects in humans. In a systematic review of&#xD;
      resveratrol research, the authors conclude that &quot;in contrast to the lacking data of&#xD;
      resveratrol in humans, the animal data are promising and indicate the need for further human&#xD;
      clinical trials.&quot; Of the small clinical studies that have been done, the results are&#xD;
      encouraging. Improvement in triglycerides, blood pressure and insulin resistance were noted.&#xD;
      Resveratrol was well tolerated without serious side effects. These studies, however, did not&#xD;
      recruit subjects with the metabolic syndrome, nor were they tightly controlled.&#xD;
&#xD;
      The investigators propose to prove that resveratrol, administered to subjects with the&#xD;
      metabolic syndrome, under controlled conditions of weight stability, common diet, and strict&#xD;
      compliance with the study drug, will improve the symptoms of the metabolic syndrome, thereby&#xD;
      decreasing the chance of developing diabetes or heart disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">August 2015</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in Insulin resistance</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Investigators anticipate resveratrol will have positive effect (ie reduction) on Insulin resistance as determined by Euglycemic hyperinsulinemic clamp</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction in serum cytokines/chemokines</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Investigators anticipate resveratrol will have positive effect (ie reduction) on Serum cytokines/chemokines: IL6, IL10, TNFalpha, hsCRP, leukocytes, PAI-1, fibrinogen, adiponectin, MCP-1,GLP-1, leptin, insulin, serum endotoxins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in blood pressure measurements</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>24 hour systolic blood pressure measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction lipid values</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Lipid values to be reviewed: cholesterol, LDL, HDL, TG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in crown like structures and adipose tissue mass</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Crown like structures in adipose tissue, and adipose tissue mass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in HOMA-IR</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Changes in 2 hr oral glucose tolerance test HOMA-IR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gene expression in adipose tissue</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Changes in RNA sequencing of adipose tissue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gene expression in stool</measure>
    <time_frame>Days 4-8 and Days 31-35</time_frame>
    <description>Changes in microbiome and RNA gene expression in stool samples</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Obesity</condition>
  <condition>Insulin Resistance</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for 30 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Resveratrol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1000 mg PO BID for 30 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo manufactured to mimic resveratrol tablet</description>
    <arm_group_label>Resveratrol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Resveratrol</intervention_name>
    <description>Resveratrol PO BID for 30 days</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 30 - 60 year old men&#xD;
&#xD;
          -  Willingness to be randomized to resveratrol or placebo.&#xD;
&#xD;
          -  BMI 30-40&#xD;
&#xD;
          -  Evidence of insulin resistance with one of the following:&#xD;
&#xD;
             2 hr oral glucose tolerance result =/&gt;120mg/dl at 2hrs acanthosis nigricans, or HgA1C&#xD;
             5.7 - 7.9%, or FBS &gt;/= 100 mg/dl AND at least 2 of the following: waist circumference&#xD;
             &gt; 102 cm triglycerides &gt; 150 but &lt; 500 mg/dL HDL &lt; 40 mg/dL Pre- hypertension or&#xD;
             hypertension: BP&gt;120/80 mmHg but &lt;150/90 mmHg&#xD;
&#xD;
          -  Willingness to consume only study food and drink during the in-pt phases&#xD;
&#xD;
          -  Willingness to avoid the use of over-the-counter medications, herbs, or supplements&#xD;
             within the last 30 days.&#xD;
&#xD;
          -  Willingness to avoid NSAIDS (advil, aleve, motrin, etc.) and aspirin for the entire&#xD;
             study&#xD;
&#xD;
          -  Willingness to avoid ingestion of any foods containing peanuts, bilberries,&#xD;
             blueberries, cranberries, strawberries, raspberries, grapes, grape juice, cocoa&#xD;
             powder, dark chocolate, and red wine throughout the entire study, including run-in&#xD;
             period.&#xD;
&#xD;
          -  Willingness to maintain weight for the duration of the study.&#xD;
&#xD;
          -  Willingness not to start an exercise regime during study participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Tobacco smoker any time within the last 3 months&#xD;
&#xD;
          -  Bleeding disorder by history or by Bleeding Questionnaire results&#xD;
&#xD;
          -  History, physical or EKG findings suggestive of CV disease including angina, MI, hx of&#xD;
             med/surg tx of atherosclerotic heart disease, or congestive heart disease&#xD;
&#xD;
          -  BP &gt; 145/90 after 10 minutes of rest on 2 or more screening visits&#xD;
&#xD;
          -  Fasting glucose &gt; 165 mg/dL at screening&#xD;
&#xD;
          -  HbA1C &gt; 8.0 at screening&#xD;
&#xD;
          -  Current use of oral hypoglycemic agents&#xD;
&#xD;
          -  Chronic glucocorticosteroid use or use of oral glucocorticosteroids for 5 days within&#xD;
             the last year (inhaled glucocorticosteroid use may be acceptable; this will be&#xD;
             determined by the PI)&#xD;
&#xD;
          -  Current use of over the counter or prescription weight loss medication&#xD;
&#xD;
          -  Current use or within the last 30 days, any cholesterol lowering medications (statins,&#xD;
             fibrates, red yeast rice, niacin).&#xD;
&#xD;
          -  Hyperthyroidism or untreated hypothyroidism&#xD;
&#xD;
          -  Obstructive sleep apnea, or significant symptoms suggestive of this condition.&#xD;
&#xD;
          -  Current use of anticoagulants&#xD;
&#xD;
          -  Known history of chronic hepatitis or liver enzymes (ALT or AST &gt; 2.5 times the normal&#xD;
             upper limit)&#xD;
&#xD;
          -  Known HIV infection or confirmed positive test for HIV antibodies at screening&#xD;
&#xD;
          -  Inflammatory bowel disease&#xD;
&#xD;
          -  Active cancer (currently under treatment)&#xD;
&#xD;
          -  Other medical condition that may cause significant weight loss or gain&#xD;
&#xD;
          -  Chronic or acute renal disease&#xD;
&#xD;
          -  Seizure disorder&#xD;
&#xD;
          -  History of any psychiatric hospital admission within the last 2 years&#xD;
&#xD;
          -  History of schizophrenia, psychosis, or bipolar disease&#xD;
&#xD;
          -  History, physical, social or lab findings suggestive of any medical or psychological&#xD;
             condition that would, in the opinion of the PI, impact the subject's ability to&#xD;
             successfully participate in the study.&#xD;
&#xD;
          -  Alcohol or drug abuse within the last 2 years&#xD;
&#xD;
          -  Any medications metabolized by cytochrome p450 3A4 (CYPA3A4) (see attachment of these&#xD;
             medications as an appendix)&#xD;
&#xD;
          -  Any autoimmune disease (ie rheumatoid arthritis, systemic lupus erythematosis,&#xD;
             psoriasis)&#xD;
&#xD;
          -  Physical condition requiring special diet (ie celiac disease)&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeanne Walker, MSN/NP-C</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Rockefeller University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Rockefeller University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 25, 2012</study_first_posted>
  <last_update_submitted>October 22, 2018</last_update_submitted>
  <last_update_submitted_qc>October 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rockefeller University</investigator_affiliation>
    <investigator_full_name>Jeanne Walker</investigator_full_name>
    <investigator_title>Senior Clinical Nurse Practitioner &amp; Research Coordinator</investigator_title>
  </responsible_party>
  <keyword>Obesity</keyword>
  <keyword>Insulin resistance</keyword>
  <keyword>Metabolic syndrome</keyword>
  <keyword>Pre-diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Insulin Resistance</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>
  <!-- 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/NCT01714102
org study id: JWA-0786
nct id: NCT01714102
lead sponsor: 
has dmc: No
Metabolic syndrome is a serious health condition that affects about 35 percent of adults and
      places them at higher risk of cardiovascular disease, diabetes, stroke and diseases related
      to fatty buildups in artery walls. The underlying causes of metabolic syndrome are obesity,
      being overweight, physical inactivity and genetic factors. In recent decades, the prevalence
      has increased dramatically in the United States. Lifestyle interventions including dietary
      modification, physical activity and weight loss form the basis of treatment for these
      patients. However, research has shown that even when people are able to incorporate these
      changes, they often revert back to their usual lifestyle resulting in weight gain and
      continued risk for diabetes and heart disease.

      Resveratrol, a natural plant derived compound found in grapes, peanuts and red wine, has been
      found to reverse some of the features of the metabolic syndrome (insulin resistance, high
      triglycerides, high blood pressure) in rodents. These improvements occurred without weight
      loss, and were proven to be a direct result of resveratrol ingestion. Other studies reveal
      improvement in cardiovascular health, tumor suppression, and longevity. However, there are
      few studies investigating these beneficial effects in humans. Investigators propose to prove
      that resveratrol, administered to subjects with the metabolic syndrome, under controlled
      conditions of weight stability, common diet, and strict compliance with the study drug, will
      improve the symptoms of the metabolic syndrome, thereby decreasing the chance of developing
      diabetes or heart disease.
The metabolic syndrome is a serious health condition that affects about 35 percent of adults
      and places them at higher risk of cardiovascular disease, diabetes, stroke and diseases
      related to fatty buildups in artery walls. The underlying causes of metabolic syndrome are
      obesity, being overweight, physical inactivity and genetic factors. In recent decades, the
      prevalence has increased dramatically in the United States. Lifestyle interventions including
      dietary modification, physical activity and weight loss form the basis of treatment for these
      patients. However, research has shown that even when people are able to incorporate these
      changes, they often revert back to their usual lifestyle resulting in weight gain and
      continued risk for diabetes and heart disease.

      Resveratrol, a natural plant derived compound found in grapes, peanuts and red wine, has been
      found to reverse some of the features of the metabolic syndrome (insulin resistance, high
      triglycerides, high blood pressure) in rodents. These improvements occurred without weight
      loss, and were proven to be a direct result of resveratrol ingestion. Other studies reveal
      improvement in cardiovascular health, tumor suppression, and longevity. However, there are
      few studies investigating these beneficial effects in humans. In a systematic review of
      resveratrol research, the authors conclude that "in contrast to the lacking data of
      resveratrol in humans, the animal data are promising and indicate the need for further human
      clinical trials." Of the small clinical studies that have been done, the results are
      encouraging. Improvement in triglycerides, blood pressure and insulin resistance were noted.
      Resveratrol was well tolerated without serious side effects. These studies, however, did not
      recruit subjects with the metabolic syndrome, nor were they tightly controlled.

      The investigators propose to prove that resveratrol, administered to subjects with the
      metabolic syndrome, under controlled conditions of weight stability, common diet, and strict
      compliance with the study drug, will improve the symptoms of the metabolic syndrome, thereby
      decreasing the chance of developing diabetes or heart disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Reduction in Insulin resistance
time frame: Days 4-8 and Days 31-35
description: Investigators anticipate resveratrol will have positive effect (ie reduction) on Insulin resistance as determined by Euglycemic hyperinsulinemic clamp
measure: Reduction in serum cytokines/chemokines
time frame: Days 4-8 and Days 31-35
description: Investigators anticipate resveratrol will have positive effect (ie reduction) on Serum cytokines/chemokines: IL6, IL10, TNFalpha, hsCRP, leukocytes, PAI-1, fibrinogen, adiponectin, MCP-1,GLP-1, leptin, insulin, serum endotoxins
measure: Reduction in blood pressure measurements
time frame: Days 4-8 and Days 31-35
description: 24 hour systolic blood pressure measurements
measure: Reduction lipid values
time frame: Days 4-8 and Days 31-35
description: Lipid values to be reviewed: cholesterol, LDL, HDL, TG
measure: Reduction in crown like structures and adipose tissue mass
time frame: Days 4-8 and Days 31-35
description: Crown like structures in adipose tissue, and adipose tissue mass
measure: Changes in HOMA-IR
time frame: Days 4-8 and Days 31-35
description: Changes in 2 hr oral glucose tolerance test HOMA-IR
measure: Changes in gene expression in adipose tissue
time frame: Days 4-8 and Days 31-35
description: Changes in RNA sequencing of adipose tissue
measure: Changes in gene expression in stool
time frame: Days 4-8 and Days 31-35
description: Changes in microbiome and RNA gene expression in stool samples
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for 30 days
arm group label: Resveratrol
arm group type: Active Comparator
description: 1000 mg PO BID for 30 days
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo manufactured to mimic resveratrol tablet
arm group label: Resveratrol
intervention type: Dietary Supplement
intervention name: Resveratrol
description: Resveratrol PO BID for 30 days
arm group label: Placebo
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeanne Walker, MSN/NP-C
role: Principal Investigator
affiliation: The Rockefeller University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Rockefeller University
investigator full name: Jeanne Walker
investigator title: Senior Clinical Nurse Practitioner & Research Coordinator
mesh term: Metabolic Syndrome
mesh term: Insulin Resistance
mesh term: Syndrome
mesh term: Resveratrol