<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/NCT03798262</url>
  </required_header>
  <id_info>
    <org_study_id>S58915</org_study_id>
    <nct_id>NCT03798262</nct_id>
  </id_info>
  <brief_title>Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Healthy Subjects</brief_title>
  <official_title>Effect of Acute and Sub-acute Administration of Gluten on Extra-intestinal and Gastrointestinal Symptoms in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will investigate the effects of acute and sub-acute administration of&#xD;
      gluten on mood, intestinal permeability, gastrointestinal symptoms and gut peptide levels in&#xD;
      healthy volunteers (HV).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Actual">April 2, 2018</completion_date>
  <primary_completion_date type="Actual">April 2, 2018</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>
    <intervention_model_description>single-blinded, randomised controlled, cross-over study</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Positive and Negative Affect Schedule</measure>
    <time_frame>At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41)</time_frame>
    <description>Change from baseline. Scores can be 'very slightly or not at all', 'a little', 'moderately', 'quite a bit', 'extremely'. Measured at day 0, day 15, day 20, day 36 and day 41.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Profile of Mood State.</measure>
    <time_frame>At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41)</time_frame>
    <description>Change from baseline. Scores are measured on the Visual Analogue Scale. The scale is ranged 0 - 10, in which 0 no occurrence of the symptom and 10 a lot occurrence of the symptom. Measured at day 0, day 15, day 20, day 36 and day 41.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The effect of gluten acutely and sub-acutely on gastrointestinal symptoms in HV measured on the visual analogue scale for gastrointestinal symptoms</measure>
    <time_frame>At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41)</time_frame>
    <description>Scores are measured on the Visual Analogue Scale. With '0' no complaints and '10' a lot of complaints (change from baseline).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of gluten acutely and sub-acutely on intestinal permeability (using the lactulose mannitol ratio)</measure>
    <time_frame>At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41)</time_frame>
    <description>Investigate change in intestinal permeability after gluten administration. In the urine we can measure the ratio lactulose/mannitol. This can be measured using High Performance Liquid Chromatography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of acute and sub-acute gluten administration on high sensitive reactive protein levels in blood samples</measure>
    <time_frame>During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)</time_frame>
    <description>Change in high sensitive reactive protein levels measured at day 0, day 21 and day 41.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of acute and sub-acute gluten administration on Lipopolysaccharide-Binding Protein levels in blood samples</measure>
    <time_frame>During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)</time_frame>
    <description>Change in lipopolysaccharide-binding protein levels measured at day 0, day 21 and day 41.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of acute and sub-acute gluten administration on Lipopolysaccharide levels in blood samples</measure>
    <time_frame>During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)</time_frame>
    <description>Change in lipopolysaccharide levels measured at day 0, day 21 and day 41.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of acute and sub-acute gluten administration on gut microbiota composition (stool samples)</measure>
    <time_frame>After test visit 0 (day 0), day 13 and day 14, after test visit 1 (day 15), day 16, 17, 18, 19 and 20, two days before test visit 3 (day 34 and 35), day 36, 37, 38, 39, 40</time_frame>
    <description>Change in gut microbiota composition (compared to day 0) with focus on: Bifidobacterium, Lactobacillus, Enterobacteriaceae, E. coli; measured in stool samples. Analyses will provide an overall view of the gut microbiota composition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of acute and sub-acute gluten administration on cortisol awakening response (saliva samples)</measure>
    <time_frame>Day before test visit 1 (day 14), test visit 1 (day 15), test visit 2 (day 21), day before test visit 3 (day 35), test visit 3 (day 36) and test visit 4 (day 41)</time_frame>
    <description>Change in cortisol levels between gluten and placebo administration (saliva samples). Measured using an ELISA assay.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy Volunteers, Gluten</condition>
  <arm_group>
    <arm_group_label>Gluten</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive 16 g of gluten acutely and afterwards 2 glutenfree muffins with 8 g of gluten for 5 days sub-acutely</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients receive 16 g of whey protein acutely and afterwards 2 glutenfree muffins for 5 days sub-acutely</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Gluten</intervention_name>
    <description>Tereos</description>
    <arm_group_label>Gluten</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Whey protein from Nestlé Healthy Science</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Mass Index (BMI) of 20 - 25 kg/m2&#xD;
&#xD;
          -  Stable body weight for at least 3 months prior to the start of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical&#xD;
&#xD;
               -  Coeliac disease (excluded either by absence of the HLA-DQ2 and HLA-DQ8 haplotype&#xD;
                  or by a normal duodenal biopsy (Marsh 0) performed at endoscopy while on a gluten&#xD;
                  containing diet in individuals expressing the HLA-DQ2 (human leukocyte antigen)&#xD;
                  or HLA-DQ8 haplotype)&#xD;
&#xD;
               -  Abdominal or thoracic surgery. Exception: appendectomy&#xD;
&#xD;
               -  Gastrointestinal, endocrine or neurological diseases&#xD;
&#xD;
               -  Cardiovascular, respiratory, renal or urinary diseases&#xD;
&#xD;
               -  Hypertension&#xD;
&#xD;
               -  Diagnosed food or drug allergies&#xD;
&#xD;
          -  Psychiatric disorders&#xD;
&#xD;
          -  Eating disorders&#xD;
&#xD;
          -  Depressive disorders&#xD;
&#xD;
          -  Anxiety disorders&#xD;
&#xD;
          -  Psychotic disorders&#xD;
&#xD;
          -  Restraint or emotional eating&#xD;
&#xD;
          -  Dieters, especially no gluten-free diet or a diet low on gluten&#xD;
&#xD;
          -  Medication on a regular basis, exception: oral contraception&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  History of cannabis use or any other drug of abuse for at least 12 months prior to the&#xD;
             study&#xD;
&#xD;
          -  Alcohol abuse (more than 21 units of alcohol for men, more than 14 units for woman per&#xD;
             week)&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Jan Tack</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TARGID</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>October 11, 2018</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>January 7, 2019</last_update_submitted>
  <last_update_submitted_qc>January 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universitaire Ziekenhuizen KU Leuven</investigator_affiliation>
    <investigator_full_name>Prof Dr Jan Tack</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <!-- 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/NCT03798262
org study id: S58915
nct id: NCT03798262
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The investigators will investigate the effects of acute and sub-acute administration of
      gluten on mood, intestinal permeability, gastrointestinal symptoms and gut peptide levels in
      healthy volunteers (HV).
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: single-blinded, randomised controlled, cross-over study
primary purpose: Basic Science
masking: Single (Participant)
measure: The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Positive and Negative Affect Schedule
time frame: At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41)
description: Change from baseline. Scores can be 'very slightly or not at all', 'a little', 'moderately', 'quite a bit', 'extremely'. Measured at day 0, day 15, day 20, day 36 and day 41.
measure: The effect of gluten acutely and sub-acutely on extraintestinal symptoms in HV measured on the Profile of Mood State.
time frame: At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41)
description: Change from baseline. Scores are measured on the Visual Analogue Scale. The scale is ranged 0 - 10, in which 0 no occurrence of the symptom and 10 a lot occurrence of the symptom. Measured at day 0, day 15, day 20, day 36 and day 41.
measure: The effect of gluten acutely and sub-acutely on gastrointestinal symptoms in HV measured on the visual analogue scale for gastrointestinal symptoms
time frame: At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 21), after test visit 3 (at day 36), after test visit 4 (at day 41)
description: Scores are measured on the Visual Analogue Scale. With '0' no complaints and '10' a lot of complaints (change from baseline).
measure: The effect of gluten acutely and sub-acutely on intestinal permeability (using the lactulose mannitol ratio)
time frame: At the beginning of test visit 0 (day 0), visit 1 (at day 15), test visit 2 (at day 20), after test visit 3 (at day 36), after test visit 4 (at day 41)
description: Investigate change in intestinal permeability after gluten administration. In the urine we can measure the ratio lactulose/mannitol. This can be measured using High Performance Liquid Chromatography
measure: Effect of acute and sub-acute gluten administration on high sensitive reactive protein levels in blood samples
time frame: During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)
description: Change in high sensitive reactive protein levels measured at day 0, day 21 and day 41.
measure: Effect of acute and sub-acute gluten administration on Lipopolysaccharide-Binding Protein levels in blood samples
time frame: During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)
description: Change in lipopolysaccharide-binding protein levels measured at day 0, day 21 and day 41.
measure: Effect of acute and sub-acute gluten administration on Lipopolysaccharide levels in blood samples
time frame: During test visit 0 (day 0), test visit 2 (at day 21), after test visit 4 (at day 41)
description: Change in lipopolysaccharide levels measured at day 0, day 21 and day 41.
measure: Effect of acute and sub-acute gluten administration on gut microbiota composition (stool samples)
time frame: After test visit 0 (day 0), day 13 and day 14, after test visit 1 (day 15), day 16, 17, 18, 19 and 20, two days before test visit 3 (day 34 and 35), day 36, 37, 38, 39, 40
description: Change in gut microbiota composition (compared to day 0) with focus on: Bifidobacterium, Lactobacillus, Enterobacteriaceae, E. coli; measured in stool samples. Analyses will provide an overall view of the gut microbiota composition.
measure: Effect of acute and sub-acute gluten administration on cortisol awakening response (saliva samples)
time frame: Day before test visit 1 (day 14), test visit 1 (day 15), test visit 2 (day 21), day before test visit 3 (day 35), test visit 3 (day 36) and test visit 4 (day 41)
description: Change in cortisol levels between gluten and placebo administration (saliva samples). Measured using an ELISA assay.
arm group label: Gluten
arm group type: Active Comparator
description: Patients receive 16 g of gluten acutely and afterwards 2 glutenfree muffins with 8 g of gluten for 5 days sub-acutely
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients receive 16 g of whey protein acutely and afterwards 2 glutenfree muffins for 5 days sub-acutely
intervention type: Other
intervention name: Gluten
description: Tereos
arm group label: Gluten
intervention type: Other
intervention name: Placebo
description: Whey protein from Nestlé Healthy Science
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: Universitaire Ziekenhuizen KU Leuven
investigator full name: Prof Dr Jan Tack
investigator title: Principal Investigator