<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/NCT01674231</url>
  </required_header>
  <id_info>
    <org_study_id>321900</org_study_id>
    <secondary_id>321900-2</secondary_id>
    <nct_id>NCT01674231</nct_id>
  </id_info>
  <brief_title>The Effects Grapes on Health Indices</brief_title>
  <official_title>Pilot Study: The Effects of Whole Grapes on Markers of Health</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, Davis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hope to learn about the effects of whole grapes, in the form of&#xD;
      freeze-dried grape powder, on markers of health. Phytochemical rich food consumption is&#xD;
      associated with protection against chronic diseases such as cardiovascular disease (CVD)&#xD;
      demonstrating the ability to modify endothelial function and lipemia, but exact causal&#xD;
      mechanisms are still not well understood. The investigators will examine metabolic and&#xD;
      mechanistic effects of consumption of whole grape powder in chronic as well as acute settings&#xD;
      in response to meal challenges by testing blood samples to determine if markers of health&#xD;
      have improved.&#xD;
&#xD;
      The central hypothesis of this project is that consumption of grapes in the form of a&#xD;
      polyphenol-rich freeze-dried whole grape powder (WGP) will attenuate chronic and meal induced&#xD;
      oxidative stress and inflammatory responses in obese individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aims are to:&#xD;
&#xD;
        1. Assess the effect of WGP compared to placebo on biomarkers of oxidative stress and&#xD;
           inflammation in obese subjects over 4 week intervention periods in a randomized,&#xD;
           cross-over, double-blind study.&#xD;
&#xD;
        2. Determine the effects of WGP compared to placebo on lipid and apolipoprotein parameters,&#xD;
           and on biomarkers endothelial dysfunction, in obese subjects.&#xD;
&#xD;
        3. Investigate and characterize the effects of WGP compared to placebo on mononuclear cells&#xD;
           (MNC) from obese subjects in response to the oxidative challenge of a high fat, high&#xD;
           carbohydrate (HFHC) meal by examining monocyte indices such as oxidant stress-related&#xD;
           transcription factors and downstream gene targets.&#xD;
&#xD;
      Health promotion and prevention of chronic diseases in the face of a continuing obesity&#xD;
      epidemic is the most pressing public health issue today. Epidemiologic evidence supports a&#xD;
      protective effect of plant food-rich dietary patterns, and an inverse relationship of fruit&#xD;
      and vegetable consumption with chronic conditions like cardiovascular disease (CVD). However,&#xD;
      the underlying causal mechanisms are not well understood. Prospective human studies examining&#xD;
      consumption of polyphenol-rich whole grapes or their components have found benefits on&#xD;
      markers of oxidative stress and blood lipids as have other food examples such as blackcurrant&#xD;
      juice and strawberries. Putative mechanisms underlying the positive actions of&#xD;
      polyphenol-rich grapes have been well described in recent reviews. A number of in-vitro cell&#xD;
      culture and in-vivo animal studies with WGP and extracts support these mechanisms. However,&#xD;
      relatively fewer human studies have been conducted examining biomarkers and potential&#xD;
      mechanisms for attenuation of chronic inflammatory responses and meal-induced postprandial&#xD;
      oxidative stress and inflammation in obese humans.&#xD;
&#xD;
      Obesity is a metabolic state recognized as being pro-inflammatory, leading to dysregulation&#xD;
      of endothelial function, glucose and lipoprotein metabolism and cardiovascular risk.&#xD;
      Consumption of high fat diets can further impair vascular reactivity in the postprandial&#xD;
      period. Circulating MNC provide a representation of the overall inflammatory status of the&#xD;
      body, which is accessible and can be used to examine mechanistic processes in response to&#xD;
      chronic and meal-induced oxidative stress. Recent literature reports have described the&#xD;
      effect of polyphenol-rich food consumption and Mediterranean diet patterns to reduce NF-κB&#xD;
      activation as well as changes in downstream inflammatory gene expression in peripheral blood&#xD;
      MNC's. Therefore, the proposed study will exploit this approach to examine short-term&#xD;
      responses to a meal challenge as well as longer-term responses to daily consumption of whole&#xD;
      grapes as assessed by plasma and mononuclear cell indices. This research will shed light on&#xD;
      oxidant stress-related transcription factors and downstream gene targets involved in the&#xD;
      anti-inflammatory effects of grape consumption in obese individuals who are at increased risk&#xD;
      of chronic diseases.&#xD;
&#xD;
      Additional scientific data is needed to understand the links between diet and health and to&#xD;
      develop effective dietary strategies to improve health outcomes, particularly in obesity. The&#xD;
      use of polyphenol-rich whole grape powder to attenuate inflammatory mediators and biomarkers&#xD;
      in blood and mononuclear cells of obese humans represents a targeted intervention approach in&#xD;
      an at-risk population. The goal for the study is to examine the link between the beneficial&#xD;
      effects of grapes as a food and health in a significant public health chronic disease. The&#xD;
      outcomes of the study design will provide preliminary data which bridges well-controlled&#xD;
      human translational research and fundamental research by examining cellular responses to&#xD;
      grape consumption in a human clinical trial. The approach will generate new and unique data&#xD;
      to extend scientific knowledge and allow for the development of a mechanistic component to a&#xD;
      human feeding intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">April 2015</completion_date>
  <primary_completion_date type="Actual">October 2014</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Decrease inflammatory markers</measure>
    <time_frame>After 4 week intervention</time_frame>
    <description>High sensitivity C reactive protein, TNF-alpha, IL-1beta, lL-6. Assessed at time 0, 1, 3, 5 hours of acute meal challenge and in fasting samples at the end of the intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decrease oxidative stress</measure>
    <time_frame>After 4 week intervention</time_frame>
    <description>Oxidized low density lipoprotein, urinary F2-isoprostane.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Increase endothelial function</measure>
    <time_frame>After 4 week intervention</time_frame>
    <description>Blood pressure, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, ESelectin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Improve lipid profile</measure>
    <time_frame>After 4 week intervention</time_frame>
    <description>Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride level, apolipoproteinA1, apolipoproteinB100.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Decrease in mononuclear cell production</measure>
    <time_frame>After 4 week intervention</time_frame>
    <description>TLR4, SOCS-3, NADPH oxidase subunit p47phox, Nrf-2, p50 subunit, IL-1β, MMP-9, MCP-1.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Obesity</condition>
  <condition>Inflammation</condition>
  <condition>Cardiovascular Disease</condition>
  <condition>Oxidative Stress</condition>
  <arm_group>
    <arm_group_label>Grape</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Grapes in the form of a Freeze-dried Whole Grape Powder. 60g freeze-dried whole grape powder with 296mg polyphenols per day for 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Grape Powder Placebo. 60g control food (matched for calories, low in polyphenols, and indistinguishable from active intervention) per day for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Grape in the form of freeze-dried whole grape powder</intervention_name>
    <description>60g freeze-dried whole grape powder with 296mg polyphenols per day for 4 weeks.</description>
    <arm_group_label>Grape</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Grape powder placebo</intervention_name>
    <description>60g control food (matched for calories, low in polyphenols, and indistinguishable from active intervention) per day for 4 weeks.</description>
    <arm_group_label>Sugar</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women 18 years of age or older in good health&#xD;
&#xD;
          -  BMI &gt;30&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smokers&#xD;
&#xD;
          -  Chronic disease, such as diabetes, cancer, and renal, liver or thyroid dysfunction&#xD;
&#xD;
          -  History of gastrointestinal disease&#xD;
&#xD;
          -  History of cardiovascular events&#xD;
&#xD;
          -  If pregnant or lactating&#xD;
&#xD;
          -  Regular users of statin drugs, aspirin, anti-inflammatory medications, antioxidants or&#xD;
             botanical supplements&#xD;
&#xD;
          -  Allergy to grapes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francene M Steinberg, PhD, RD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ragle Human Nutrition Center</name>
      <address>
        <city>Davis</city>
        <state>California</state>
        <zip>95616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>May 25, 2017</last_update_submitted>
  <last_update_submitted_qc>May 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_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/NCT01674231
org study id: 321900
secondary id: 321900-2
nct id: NCT01674231
lead sponsor: 
has dmc: No
The investigators hope to learn about the effects of whole grapes, in the form of
      freeze-dried grape powder, on markers of health. Phytochemical rich food consumption is
      associated with protection against chronic diseases such as cardiovascular disease (CVD)
      demonstrating the ability to modify endothelial function and lipemia, but exact causal
      mechanisms are still not well understood. The investigators will examine metabolic and
      mechanistic effects of consumption of whole grape powder in chronic as well as acute settings
      in response to meal challenges by testing blood samples to determine if markers of health
      have improved.

      The central hypothesis of this project is that consumption of grapes in the form of a
      polyphenol-rich freeze-dried whole grape powder (WGP) will attenuate chronic and meal induced
      oxidative stress and inflammatory responses in obese individuals.
The specific aims are to:

        1. Assess the effect of WGP compared to placebo on biomarkers of oxidative stress and
           inflammation in obese subjects over 4 week intervention periods in a randomized,
           cross-over, double-blind study.

        2. Determine the effects of WGP compared to placebo on lipid and apolipoprotein parameters,
           and on biomarkers endothelial dysfunction, in obese subjects.

        3. Investigate and characterize the effects of WGP compared to placebo on mononuclear cells
           (MNC) from obese subjects in response to the oxidative challenge of a high fat, high
           carbohydrate (HFHC) meal by examining monocyte indices such as oxidant stress-related
           transcription factors and downstream gene targets.

      Health promotion and prevention of chronic diseases in the face of a continuing obesity
      epidemic is the most pressing public health issue today. Epidemiologic evidence supports a
      protective effect of plant food-rich dietary patterns, and an inverse relationship of fruit
      and vegetable consumption with chronic conditions like cardiovascular disease (CVD). However,
      the underlying causal mechanisms are not well understood. Prospective human studies examining
      consumption of polyphenol-rich whole grapes or their components have found benefits on
      markers of oxidative stress and blood lipids as have other food examples such as blackcurrant
      juice and strawberries. Putative mechanisms underlying the positive actions of
      polyphenol-rich grapes have been well described in recent reviews. A number of in-vitro cell
      culture and in-vivo animal studies with WGP and extracts support these mechanisms. However,
      relatively fewer human studies have been conducted examining biomarkers and potential
      mechanisms for attenuation of chronic inflammatory responses and meal-induced postprandial
      oxidative stress and inflammation in obese humans.

      Obesity is a metabolic state recognized as being pro-inflammatory, leading to dysregulation
      of endothelial function, glucose and lipoprotein metabolism and cardiovascular risk.
      Consumption of high fat diets can further impair vascular reactivity in the postprandial
      period. Circulating MNC provide a representation of the overall inflammatory status of the
      body, which is accessible and can be used to examine mechanistic processes in response to
      chronic and meal-induced oxidative stress. Recent literature reports have described the
      effect of polyphenol-rich food consumption and Mediterranean diet patterns to reduce NF-κB
      activation as well as changes in downstream inflammatory gene expression in peripheral blood
      MNC's. Therefore, the proposed study will exploit this approach to examine short-term
      responses to a meal challenge as well as longer-term responses to daily consumption of whole
      grapes as assessed by plasma and mononuclear cell indices. This research will shed light on
      oxidant stress-related transcription factors and downstream gene targets involved in the
      anti-inflammatory effects of grape consumption in obese individuals who are at increased risk
      of chronic diseases.

      Additional scientific data is needed to understand the links between diet and health and to
      develop effective dietary strategies to improve health outcomes, particularly in obesity. The
      use of polyphenol-rich whole grape powder to attenuate inflammatory mediators and biomarkers
      in blood and mononuclear cells of obese humans represents a targeted intervention approach in
      an at-risk population. The goal for the study is to examine the link between the beneficial
      effects of grapes as a food and health in a significant public health chronic disease. The
      outcomes of the study design will provide preliminary data which bridges well-controlled
      human translational research and fundamental research by examining cellular responses to
      grape consumption in a human clinical trial. The approach will generate new and unique data
      to extend scientific knowledge and allow for the development of a mechanistic component to a
      human feeding intervention.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Decrease inflammatory markers
time frame: After 4 week intervention
description: High sensitivity C reactive protein, TNF-alpha, IL-1beta, lL-6. Assessed at time 0, 1, 3, 5 hours of acute meal challenge and in fasting samples at the end of the intervention.
measure: Decrease oxidative stress
time frame: After 4 week intervention
description: Oxidized low density lipoprotein, urinary F2-isoprostane.
measure: Increase endothelial function
time frame: After 4 week intervention
description: Blood pressure, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, ESelectin.
measure: Improve lipid profile
time frame: After 4 week intervention
description: Total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglyceride level, apolipoproteinA1, apolipoproteinB100.
measure: Decrease in mononuclear cell production
time frame: After 4 week intervention
description: TLR4, SOCS-3, NADPH oxidase subunit p47phox, Nrf-2, p50 subunit, IL-1β, MMP-9, MCP-1.
arm group label: Grape
arm group type: Active Comparator
description: Grapes in the form of a Freeze-dried Whole Grape Powder. 60g freeze-dried whole grape powder with 296mg polyphenols per day for 4 weeks.
arm group label: Sugar
arm group type: Placebo Comparator
description: Grape Powder Placebo. 60g control food (matched for calories, low in polyphenols, and indistinguishable from active intervention) per day for 4 weeks.
intervention type: Other
intervention name: Grape in the form of freeze-dried whole grape powder
description: 60g freeze-dried whole grape powder with 296mg polyphenols per day for 4 weeks.
arm group label: Grape
intervention type: Other
intervention name: Grape powder placebo
description: 60g control food (matched for calories, low in polyphenols, and indistinguishable from active intervention) per day for 4 weeks.
arm group label: Sugar
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Francene M Steinberg, PhD, RD
role: Principal Investigator
affiliation: University of California, Davis
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cardiovascular Diseases
mesh term: Inflammation