<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/NCT01719913</url>
  </required_header>
  <id_info>
    <org_study_id>NNF-CBMR 3861-34275</org_study_id>
    <nct_id>NCT01719913</nct_id>
  </id_info>
  <brief_title>The Effect of Gluten on Gut Microbiome and Metabolic Health.</brief_title>
  <acronym>3G</acronym>
  <official_title>Gut, Grain and Greens (3G): The Effect of Gluten 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 gluten 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 interventions periods, separated by a 6-week wash-out period. A total number of 60&#xD;
      participants will be included.&#xD;
&#xD;
      Intervention: low vs high gluten 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 gluten-poor diet (&lt;5 g/d) in the active treatment period and a gluten-rich diet (&gt;25&#xD;
      g/d) during the control period.&#xD;
&#xD;
      Measurements: Altered quantitative metagenomics at bacterial gene- and species levels is the&#xD;
      primary outcome of this study. Secondary outcomes include metabolic and inflammatory markers,&#xD;
      circulating appetite hormone levels,serum metabolomics, gastrointestinal transit time and&#xD;
      intestinal permeability. Furthermore, selected control measures are included; 4-day food&#xD;
      records and a study intervention dietary records.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Altered quantitative metagenomics at bacterial gene- and species levels.</measure>
    <time_frame>Up to 3 years.</time_frame>
    <description>Feces samples are collected according to standard operation procedures for subsequent standardized microbial DNA extraction. Microbial DNA will be subjected to sequencing, microbial gene analyses, taxonomy analyses including enterotypes known species and unknown meta-species and functional annotation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean intestinal transit time</measure>
    <time_frame>Up to 2 years.</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.</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Lactulose/mannitol ratio in urine after four hours collection following oral intake of lactulose and mannitol.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Colonic fermentation</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Breath hydrogen after intake of standardized breakfast (30,60,90,120,180 minutes)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure and pulse.</measure>
    <time_frame>Up to 1 year.</time_frame>
    <description>Systolic and diastolic blood pressure and heart beat rate are measured after 10 min of rest according to current standard operational procedure with an automatic blood pressure meter. Participants are instructed not to talk during the measurements.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva microbial flora</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Saliva is collected after the participants have taken a small piece of paraffin in their mouth and have chewed until the paraffin has turned into one coherent mass (approximately one minute). Participants are swallowing the produced saliva for that minute. After this, and for the next 3 minutes, saliva is collected in a cup and handed over to the study personnel. Saliva is stored at minus 80 degrees for later studies of saliva microbial flora and saliva biochemistry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal fluid</measure>
    <time_frame>Up to 3 years.</time_frame>
    <description>Nasal fluid is collected by a non-invasive methodology for in vivo measurement of an array of immunological signalling molecules in the nasal airway lining. The method is based on a standardized collection of mucosal airway fluid from both nostrils onto small sheets of filter papers with efficient absorption properties. The technique is highly reproducible, and used for measuring immunological mediators representing the immediate response ability of the mucosal immune system.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite hormones</measure>
    <time_frame>Up to 3 years.</time_frame>
    <description>Glucagon like peptide 1 and 2, Gastric inhibitory polypeptide, peptide YY and Ghrelin.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Celiac disease markers</measure>
    <time_frame>Up to 1 year.</time_frame>
    <description>Levels of gliadin and Immunoglobulin A and G transglutaminase.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood lipid profile</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Low density Lipoproteins, High density lipoproteins, Total Cholesterol, Very low density lipoproteins and Free fatty acids.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioimpedance</measure>
    <time_frame>Up to 1 year.</time_frame>
    <description>Body composition (lean body mass and fat mass) is measured by bio-electrical impedance using multi frequency Quadscan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breath hydrogen.</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Breath hydrogen measurements are done before the intake of the standardized breakfast (at 30, 60, 90, 120, 180 minutes), as an indicator of colonic fermentation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Fasting insulin and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Fasting glucose and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-peptide</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Fasting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory makers</measure>
    <time_frame>Up to 3 years.</time_frame>
    <description>High sensitive C-reactive protein, Interleukin 1, 6 and 10, Lipopolysaccharide- binding protein, Tumor necrosis factor - alfa.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anthropometric characteristics.</measure>
    <time_frame>Up to 1 year.</time_frame>
    <description>Weight, height, sagittal height and waist circumference.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>4 days precoded food diary.</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Validated method for dietary registration, based on 2 week and 2 weekend days.</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal symptoms.</measure>
    <time_frame>Up to 2 years.</time_frame>
    <description>Changes from baseline to after intervention in individual gastrointestinal symptoms by validated VAS-questionary.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Metabolic Diseases</condition>
  <condition>Injury of Gastrointestinal Tract</condition>
  <arm_group>
    <arm_group_label>Low gluten</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Poor gluten diet: Participants consume less than 5g gluten per day (estimated to correspond to a gluten intake below the 10th percentile in the population)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High gluten</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Refined grain/ gluten rich diet : Participants consume more than 25g of gluten per day (estimated to correspond to a gluten intake around the 90th percentile in the population)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High gluten</intervention_name>
    <description>Refined grain/ gluten rich diet : Participants consume more than 25g of gluten per day (estimated to correspond to a gluten intake around the 90th percentile in the population)</description>
    <arm_group_label>High gluten</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Low gluten</intervention_name>
    <description>Poor gluten diet: Participants consume less than 5g gluten per day (estimated to correspond to a gluten intake below the 10th percentile in the population)</description>
    <arm_group_label>Low gluten</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria, compulsory:&#xD;
&#xD;
          -  Body mass index (BMI): 25 - 35 kg/m2 OR&#xD;
&#xD;
          -  Abdominal obesity: waist circumference: men: ≥ 94cm; women: ≥ 80cm&#xD;
&#xD;
          -  No medically prescribed diet&#xD;
&#xD;
          -  Weight stable&#xD;
&#xD;
          -  Intense sporting activities less than 10 h/week&#xD;
&#xD;
          -  Alcohol consumption less than 14 units/week (female) and 21 units/week (male)&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Inclusion criteria, minimum one of the following:&#xD;
&#xD;
          -  Fasting plasma glucose from 6.1 mmol/l to 6.9 mmol/l&#xD;
&#xD;
          -  Reduced high density lipoprotein (HDL) cholesterol; HDL ≤ 1.03 mmol/L for men and ≤&#xD;
             1.29 mmol/L for women&#xD;
&#xD;
          -  Increased triglyceride (TG) &gt; 1.3 mmol/L&#xD;
&#xD;
          -  Systolic blood pressure &gt; 130 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pharmacological treatment; 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;
          -  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>Oluf B Pedersen, MD, DMSCi,Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Copenhagen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Novo Nordisk Foundation of Basic Metabolic Health, Section for Metabolic Genetics</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</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>December 2013</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 1, 2012</study_first_posted>
  <last_update_submitted>December 4, 2013</last_update_submitted>
  <last_update_submitted_qc>December 4, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 5, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Oluf Borbye Pedersen</investigator_full_name>
    <investigator_title>Scientific Director, 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/NCT01719913
org study id: NNF-CBMR 3861-34275
nct id: NCT01719913
lead sponsor: 
collaborator: 
has dmc: Yes
Objective: To identify how specific changes of the gluten 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 interventions periods, separated by a 6-week wash-out period. A total number of 60
      participants will be included.

      Intervention: low vs high gluten 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 gluten-poor diet (<5 g/d) in the active treatment period and a gluten-rich diet (>25
      g/d) during the control period.

      Measurements: Altered quantitative metagenomics at bacterial gene- and species levels is the
      primary outcome of this study. Secondary outcomes include metabolic and inflammatory markers,
      circulating appetite hormone levels,serum metabolomics, gastrointestinal transit time and
      intestinal permeability. Furthermore, selected control measures are included; 4-day food
      records and a study intervention dietary records.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: Altered quantitative metagenomics at bacterial gene- and species levels.
time frame: Up to 3 years.
description: Feces samples are collected according to standard operation procedures for subsequent standardized microbial DNA extraction. Microbial DNA will be subjected to sequencing, microbial gene analyses, taxonomy analyses including enterotypes known species and unknown meta-species and functional annotation.
measure: Mean intestinal transit time
time frame: Up to 2 years.
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.
time frame: Up to 2 years.
description: Lactulose/mannitol ratio in urine after four hours collection following oral intake of lactulose and mannitol.
measure: Colonic fermentation
time frame: Up to 2 years.
description: Breath hydrogen after intake of standardized breakfast (30,60,90,120,180 minutes)
measure: Blood pressure and pulse.
time frame: Up to 1 year.
description: Systolic and diastolic blood pressure and heart beat rate are measured after 10 min of rest according to current standard operational procedure with an automatic blood pressure meter. Participants are instructed not to talk during the measurements.
measure: Saliva microbial flora
time frame: Up to 2 years.
description: Saliva is collected after the participants have taken a small piece of paraffin in their mouth and have chewed until the paraffin has turned into one coherent mass (approximately one minute). Participants are swallowing the produced saliva for that minute. After this, and for the next 3 minutes, saliva is collected in a cup and handed over to the study personnel. Saliva is stored at minus 80 degrees for later studies of saliva microbial flora and saliva biochemistry.
measure: Nasal fluid
time frame: Up to 3 years.
description: Nasal fluid is collected by a non-invasive methodology for in vivo measurement of an array of immunological signalling molecules in the nasal airway lining. The method is based on a standardized collection of mucosal airway fluid from both nostrils onto small sheets of filter papers with efficient absorption properties. The technique is highly reproducible, and used for measuring immunological mediators representing the immediate response ability of the mucosal immune system.
measure: Appetite hormones
time frame: Up to 3 years.
description: Glucagon like peptide 1 and 2, Gastric inhibitory polypeptide, peptide YY and Ghrelin.
measure: Celiac disease markers
time frame: Up to 1 year.
description: Levels of gliadin and Immunoglobulin A and G transglutaminase.
measure: Blood lipid profile
time frame: Up to 2 years.
description: Low density Lipoproteins, High density lipoproteins, Total Cholesterol, Very low density lipoproteins and Free fatty acids.
measure: Bioimpedance
time frame: Up to 1 year.
description: Body composition (lean body mass and fat mass) is measured by bio-electrical impedance using multi frequency Quadscan.
measure: Breath hydrogen.
time frame: Up to 2 years.
description: Breath hydrogen measurements are done before the intake of the standardized breakfast (at 30, 60, 90, 120, 180 minutes), as an indicator of colonic fermentation.
measure: Insulin
time frame: Up to 2 years.
description: Fasting insulin and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.
measure: Glucose
time frame: Up to 2 years.
description: Fasting glucose and post prandial at 30, 60, 90, 120 and 180 minutes after standardized meal.
measure: C-peptide
time frame: Up to 2 years.
description: Fasting.
measure: Inflammatory makers
time frame: Up to 3 years.
description: High sensitive C-reactive protein, Interleukin 1, 6 and 10, Lipopolysaccharide- binding protein, Tumor necrosis factor - alfa.
measure: Anthropometric characteristics.
time frame: Up to 1 year.
description: Weight, height, sagittal height and waist circumference.
measure: 4 days precoded food diary.
time frame: Up to 2 years.
description: Validated method for dietary registration, based on 2 week and 2 weekend days.
measure: Gastrointestinal symptoms.
time frame: Up to 2 years.
description: Changes from baseline to after intervention in individual gastrointestinal symptoms by validated VAS-questionary.
arm group label: Low gluten
arm group type: Active Comparator
description: Poor gluten diet: Participants consume less than 5g gluten per day (estimated to correspond to a gluten intake below the 10th percentile in the population)
arm group label: High gluten
arm group type: Placebo Comparator
description: Refined grain/ gluten rich diet : Participants consume more than 25g of gluten per day (estimated to correspond to a gluten intake around the 90th percentile in the population)
intervention type: Other
intervention name: High gluten
description: Refined grain/ gluten rich diet : Participants consume more than 25g of gluten per day (estimated to correspond to a gluten intake around the 90th percentile in the population)
arm group label: High gluten
intervention type: Other
intervention name: Low gluten
description: Poor gluten diet: Participants consume less than 5g gluten per day (estimated to correspond to a gluten intake below the 10th percentile in the population)
arm group label: Low gluten
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Oluf B Pedersen, MD, DMSCi,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: Oluf Borbye Pedersen
investigator title: Scientific Director, professor
mesh term: Metabolic Diseases