<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/NCT01731366</url>
  </required_header>
  <id_info>
    <org_study_id>M206</org_study_id>
    <nct_id>NCT01731366</nct_id>
  </id_info>
  <brief_title>The Effect of Whole Grain on Gut Microbiome and Metabolic Health</brief_title>
  <acronym>3G</acronym>
  <official_title>Gut, Grain and Greens (3G): The Effect of Wholegrain on Gut Microbiome and Metabolic Health</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Technical University of Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Copenhagen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objective: To identify how specific changes of the whole grain content in the diet affect the&#xD;
      host-gut microbiome interactions with implications for metabolic health .&#xD;
&#xD;
      Design: A randomized, controlled, single-blinded, cross-over intervention trial consisting of&#xD;
      two 8-week intervention periods, separated by a 6-week wash-out period. A total of 60&#xD;
      participants will be included.&#xD;
&#xD;
      Intervention: low vs. high whole grain intake.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study is designed as a randomized, controlled, single-blinded, cross-over intervention&#xD;
      trial consisting of two 8-week interventions periods, separated by a 6-week wash-out period.&#xD;
      A total number of 60 participants will be included. Participants consume, in randomized&#xD;
      order, a diet rich in whole grain in the active treatment period and a refined grain diet&#xD;
      during the control period.&#xD;
&#xD;
      Measurements: Insulin sensitivity will be assessed by means of a meal challenge test and by&#xD;
      the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) which is the primary outcome&#xD;
      of this study. Secondary outcomes include metabolic and inflammatory markers, appetite&#xD;
      hormones, transit time, and GM composition. Furthermore, selected control measures are&#xD;
      included; 4-day food records and a study intervention diary.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Actual">February 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>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HOMA-IR</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Homeostasis Model Assessment of fasting Insulin Resistance (HOMA-IR: glucose (mmol/l( x insulin (pmol/l)/22.5)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Metagenomic profile</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Altered quantitative metagenomics at bacterial gene- and species levels, which is a non-specific outcome, but included as the main hypothesis of the project is to test if HOMA-IR is affected via changes in the gut microbiome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean intestinal transit time</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Participants are instructed in swallowing capsules containing different small non-invasive and non-absorbable plastic pellets for 6 consecutive days. On the seventh day they are having an X-ray of the abdomen taken.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal permeability, Lactulose/ mannitol ratio</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>5 hours urine collection following intake of lactulose and mannitol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colonic fermentation</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Measurement of breath hydrogen excretion (at before and 30, 60, 90, 120, 150, 180 after intake of standard breakfast) and plasma short-chain fatty acids (fasting and 30, 60, 120, 180 minutes after standard breakfast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva microbial flora</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Determination of fasting microbial composition of flora.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Measurement of supine systolic and diastolic blood pressure (3 times)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite hormones</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Determination of different appetite hormones in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood lipid profile</measure>
    <time_frame>At the end of the interventions periods</time_frame>
    <description>Measurement of different blood lipids in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body composition</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Measurement of body fat mass and percentage via bio-impedance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective appetite sensation</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessment of subjective appetite sensation via visual analogue scales</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Energy intake</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ex vivo cytokine production</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Production of cytokines (such as IL-1beta, IL-6) in stimulated whole blood cultures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene expression</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessed by mRNA qPCR in whole blood and cells from whole blood stimulation. Main focus is put on genes involved in immune function and metabolic regulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune cell profiling</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessed by flow cytometry of whole blood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune markers</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Fasting plasma cytokines, hsCRP, and LPS/LPS-BP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood immune cell content</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessed by hematological cell counts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers og glucose hemostasis</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of one-carbon metabolism</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessed by plasma homocystein, SAM/SAH and betain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma adipokines</measure>
    <time_frame>December 2015</time_frame>
    <description>Leptin and adiponectin</description>
  </secondary_outcome>
  <other_outcome>
    <measure>4-days precoded food diary</measure>
    <time_frame>December 2014</time_frame>
    <description>Assessment of dietary intake via food frequency questionnaire as a measure of compliance</description>
  </other_outcome>
  <other_outcome>
    <measure>n-3 fatty acid status</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Assessed as DHA percentage in a whole blood fatty acid analysis. Included as a potential effect modificator in relation to immune function and metabolic outcomes.</description>
  </other_outcome>
  <other_outcome>
    <measure>Alkyresorcinol</measure>
    <time_frame>At the end of the intervention periods</time_frame>
    <description>Measured in plasma as a marker of compliance to the whole grain intervention.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Metabolic Disease</condition>
  <condition>Injury of Gastrointestinal Tract</condition>
  <arm_group>
    <arm_group_label>Refined grain</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Whole grain</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Whole grain</intervention_name>
    <description>Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)</description>
    <arm_group_label>Whole grain</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Refined grain</intervention_name>
    <description>Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)</description>
    <arm_group_label>Refined grain</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI): 25 - 35 kg/m2&#xD;
&#xD;
          -  No medical prescribed diet&#xD;
&#xD;
          -  Weight stable&#xD;
&#xD;
          -  No blood donation during the study&#xD;
&#xD;
          -  Intense sporting activities less than 10h/ week&#xD;
&#xD;
          -  Alcohol consumption less than 14 units/ week (female) and 21 units/ week (male)&#xD;
&#xD;
          -  Signed written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pharmacological treatment; hypertension, diabetes and blood lipid regulation&#xD;
&#xD;
          -  Lactating (or lactating, 6 weeks ago), pregnant (or pregnant, 3 months ago) or wish to&#xD;
             become pregnant during the study&#xD;
&#xD;
          -  Participation in another biomedical trial 1 month prior to study start&#xD;
&#xD;
          -  Diagnosed with any form of diabetes, celiac disease or chronic pancreatitis&#xD;
&#xD;
          -  Reported chronic gastrointestinal disorders&#xD;
&#xD;
          -  Antibiotic treatment for 3 month prior to study start&#xD;
&#xD;
          -  Intake of vitamin, mineral, or pre- or probiotic supplements for 1 month prior to&#xD;
             study start&#xD;
&#xD;
          -  Blood hemoglobin &lt; 7.0 mmol/l&#xD;
&#xD;
          -  Blood donation within 1 month prior to study start&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lotte Lauritzen, Associate professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Copenhagen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Human Nutrition, University of Copenhagen</name>
      <address>
        <city>Fredriksberg</city>
        <zip>1958</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://www.3g-center.dk/</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>September 1, 2014</last_update_submitted>
  <last_update_submitted_qc>September 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 3, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Arne Astrup</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Diseases</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/NCT01731366
org study id: M206
nct id: NCT01731366
lead sponsor: 
collaborator: 
has dmc: Yes
Objective: To identify how specific changes of the whole grain content in the diet affect the
      host-gut microbiome interactions with implications for metabolic health .

      Design: A randomized, controlled, single-blinded, cross-over intervention trial consisting of
      two 8-week intervention periods, separated by a 6-week wash-out period. A total of 60
      participants will be included.

      Intervention: low vs. high whole grain intake.
The study is designed as a randomized, controlled, single-blinded, cross-over intervention
      trial consisting of two 8-week interventions periods, separated by a 6-week wash-out period.
      A total number of 60 participants will be included. Participants consume, in randomized
      order, a diet rich in whole grain in the active treatment period and a refined grain diet
      during the control period.

      Measurements: Insulin sensitivity will be assessed by means of a meal challenge test and by
      the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) which is the primary outcome
      of this study. Secondary outcomes include metabolic and inflammatory markers, appetite
      hormones, transit time, and GM composition. Furthermore, selected control measures are
      included; 4-day food records and a study intervention diary.
allocation: Randomized
intervention model: Crossover Assignment
masking: Single (Investigator)
measure: HOMA-IR
time frame: At the end of the intervention periods
description: Homeostasis Model Assessment of fasting Insulin Resistance (HOMA-IR: glucose (mmol/l( x insulin (pmol/l)/22.5)
measure: Metagenomic profile
time frame: At the end of the intervention periods
description: Altered quantitative metagenomics at bacterial gene- and species levels, which is a non-specific outcome, but included as the main hypothesis of the project is to test if HOMA-IR is affected via changes in the gut microbiome.
measure: Mean intestinal transit time
time frame: At the end of the intervention periods
description: Participants are instructed in swallowing capsules containing different small non-invasive and non-absorbable plastic pellets for 6 consecutive days. On the seventh day they are having an X-ray of the abdomen taken.
measure: Gastrointestinal permeability, Lactulose/ mannitol ratio
time frame: At the end of the intervention periods
description: 5 hours urine collection following intake of lactulose and mannitol
measure: Colonic fermentation
time frame: At the end of the intervention periods
description: Measurement of breath hydrogen excretion (at before and 30, 60, 90, 120, 150, 180 after intake of standard breakfast) and plasma short-chain fatty acids (fasting and 30, 60, 120, 180 minutes after standard breakfast)
measure: Saliva microbial flora
time frame: At the end of the intervention periods
description: Determination of fasting microbial composition of flora.
measure: Blood pressure
time frame: At the end of the intervention periods
description: Measurement of supine systolic and diastolic blood pressure (3 times)
measure: Appetite hormones
time frame: At the end of the intervention periods
description: Determination of different appetite hormones in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)
measure: Blood lipid profile
time frame: At the end of the interventions periods
description: Measurement of different blood lipids in fasting and postprandial blood samples (30, 60, 120, 180 minutes after standard breakfast)
measure: Body composition
time frame: At the end of the intervention periods
description: Measurement of body fat mass and percentage via bio-impedance
measure: Subjective appetite sensation
time frame: At the end of the intervention periods
description: Assessment of subjective appetite sensation via visual analogue scales
measure: Energy intake
time frame: At the end of the intervention periods
description: Assessment of energy intake at an ad libitum meal 3 hours after a standard breakfast
measure: Ex vivo cytokine production
time frame: At the end of the intervention periods
description: Production of cytokines (such as IL-1beta, IL-6) in stimulated whole blood cultures.
measure: Gene expression
time frame: At the end of the intervention periods
description: Assessed by mRNA qPCR in whole blood and cells from whole blood stimulation. Main focus is put on genes involved in immune function and metabolic regulation.
measure: Immune cell profiling
time frame: At the end of the intervention periods
description: Assessed by flow cytometry of whole blood.
measure: Immune markers
time frame: At the end of the intervention periods
description: Fasting plasma cytokines, hsCRP, and LPS/LPS-BP
measure: Blood immune cell content
time frame: At the end of the intervention periods
description: Assessed by hematological cell counts
measure: Markers og glucose hemostasis
time frame: At the end of the intervention periods
description: Measurement of plasma concentrations of Insulin, Proinsulin and HbA1c
measure: Markers of one-carbon metabolism
time frame: At the end of the intervention periods
description: Assessed by plasma homocystein, SAM/SAH and betain
measure: Plasma adipokines
time frame: December 2015
description: Leptin and adiponectin
measure: 4-days precoded food diary
time frame: December 2014
description: Assessment of dietary intake via food frequency questionnaire as a measure of compliance
measure: n-3 fatty acid status
time frame: At the end of the intervention periods
description: Assessed as DHA percentage in a whole blood fatty acid analysis. Included as a potential effect modificator in relation to immune function and metabolic outcomes.
measure: Alkyresorcinol
time frame: At the end of the intervention periods
description: Measured in plasma as a marker of compliance to the whole grain intervention.
arm group label: Refined grain
arm group type: Placebo Comparator
description: Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)
arm group label: Whole grain
arm group type: Active Comparator
description: Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)
intervention type: Other
intervention name: Whole grain
description: Whole grain diet: Participants consume more than 75g of whole grain per day (corresponds to the whole grain intake of the 90th percentile of the population)
arm group label: Whole grain
intervention type: Other
intervention name: Refined grain
description: Refined grain diet: Participants consume less than 10 g of whole grain per day (corresponds to the whole grain intake below the 10th percentile of the population)
arm group label: Refined grain
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lotte Lauritzen, Associate professor
role: Principal Investigator
affiliation: University of Copenhagen
facility: 
country: Denmark
url: http://www.3g-center.dk/
description: Related Info
responsible party type: Principal Investigator
investigator affiliation: University of Copenhagen
investigator full name: Arne Astrup
investigator title: Professor
mesh term: Metabolic Diseases