<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/NCT04401956</url>
  </required_header>
  <id_info>
    <org_study_id>ErnMed-Brot</org_study_id>
    <nct_id>NCT04401956</nct_id>
  </id_info>
  <brief_title>Bread Study: Comparison of the Tolerance of Spelt and Wheat Bread</brief_title>
  <official_title>Comparison of the Tolerance of Spelt and Wheat Bread in Humans With Suspected NCWS Considering Different Manufacturing Processes of Bread</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Hohenheim</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Hohenheim</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>
      This project aims to verify the hypothesis that spelt products are more tolerable than bread&#xD;
      wheat products in a target group of individuals with self-diagnosed wheat sensitivity. In&#xD;
      addition, the influence of different manufacturing processes will be considered.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Wheat cereals are known to be capable of triggering wheat allergy and celiac disease. The&#xD;
      prevalence of both diseases is about 1%. Recently, another clinical entity was described, the&#xD;
      non-celiac wheat sensitivity (NCWS). The origin and mechanisms of NCWS are unclear at&#xD;
      present, but the existence of this new disease entity has been proven by double-blind&#xD;
      placebo-controlled challenge tests. Three different grain components have been proposed as&#xD;
      triggers of NCWS, gluten, α-amylase trypsin inhibitors or fermentable carbohydrates&#xD;
      (FODMAPs).&#xD;
&#xD;
      It is reported that individuals with self-diagnosed NCWS quite often tolerate spelt products&#xD;
      much better, even though spelt shows a higher gluten content than bread wheat products.&#xD;
      Therefore, the question arises whether this putative spelt tolerance can be confirmed on an&#xD;
      objective basis and whether the underlying molecular mechanisms can be elucidated. So far,&#xD;
      human study addressing such questions are lacking.&#xD;
&#xD;
      This project aims to verify the hypothesis that spelt products are more tolerable than bread&#xD;
      wheat products in a target group of individuals with self-diagnosed wheat sensitivity. In&#xD;
      addition, the influence of different manufacturing processes on wheat sensitivity will be&#xD;
      revealed.&#xD;
&#xD;
      For this purpose, the trial involves individuals with self-diagnosed wheat sensitivity and&#xD;
      spelt tolerance. Six different kinds of bread will be tested, including 4 wheat and spelt&#xD;
      breads, each of them produced following a traditional or a conventional way. Aim of this part&#xD;
      is to objective bread wheat and spelt intolerance in a defined population. To find out&#xD;
      whether FODMAPs or gluten affect the tolerance of bread, two additional breads will be&#xD;
      tested, a gluten-free bread with added gluten and a gluten-free bread with added FODMAPs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 15, 2020</start_date>
  <completion_date type="Actual">September 7, 2021</completion_date>
  <primary_completion_date type="Actual">August 10, 2021</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>Supportive Care</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of IBS-SSS Total score</measure>
    <time_frame>Study examinations are at baseline, after wash out phases (day 3, 10, 17, 24, 31, 38) and after bread intervention phases (day 7, 14, 21, 28, 35, 42).)</time_frame>
    <description>IBS-SSS Total score will be collected with a questionnaire</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Extraintestinal Symptoms</measure>
    <time_frame>Study examinations are at baseline, after wash out phases (day 3, 10, 17, 24, 31, 38) and after bread intervention phases (day 7, 14, 21, 28, 35, 42).)</time_frame>
    <description>The study team will ask the participants for typical extraintestinal symptoms in NCWS like headache, foggy-mind, nausea, heartburn, exhaustion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood and fecal markers</measure>
    <time_frame>Study examinations are at baseline and after bread intervention phases (day 7, 14, 21, 28, 35, 42).</time_frame>
    <description>Change of blood- and fecal markers that will reveal inflammation or intestinal permeability (Anti-gliadin Immunglobulin G antibody, lipase, ferritin, zonulin, calprotectin and lactoferrin)</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Non-celiac Gluten Sensitivity</condition>
  <condition>Wheat Intolerance</condition>
  <arm_group>
    <arm_group_label>Gluten free bread with added gluten</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Gluten free bread with added FODMAPs</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Traditional manufactured wheat bread</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Traditional manufactured spelt bread</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional manufactured wheat bread</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional manufactured spelt bread</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bread will be eaten by the participants for 4 consecutive days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>bread</intervention_name>
    <description>Different types of bread</description>
    <arm_group_label>Conventional manufactured spelt bread</arm_group_label>
    <arm_group_label>Conventional manufactured wheat bread</arm_group_label>
    <arm_group_label>Gluten free bread with added FODMAPs</arm_group_label>
    <arm_group_label>Gluten free bread with added gluten</arm_group_label>
    <arm_group_label>Traditional manufactured spelt bread</arm_group_label>
    <arm_group_label>Traditional manufactured wheat bread</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 ≤70 years&#xD;
&#xD;
          -  Signed declaration of consent&#xD;
&#xD;
          -  Willingness to adhere to the prescribed diet for the duration of the study&#xD;
&#xD;
          -  Subjective bread wheat intolerance&#xD;
&#xD;
          -  No known spelled intolerance&#xD;
&#xD;
          -  No acute or chronic gastrointestinal diseases (e.g. celiac disease / wheat allergy)&#xD;
&#xD;
          -  No participation in another clinical trial (current or within the past 30 days)&#xD;
&#xD;
          -  Gluten-containing diet at least 6 weeks before the start of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Taking intestinal therapeutics, antibiotics, immunosuppressants or similar&#xD;
&#xD;
          -  Pregnancy / lactation&#xD;
&#xD;
          -  Relevant violations of the nutritional protocol&#xD;
&#xD;
          -  Occurrence of relevant diseases (possibly individual decision)&#xD;
&#xD;
          -  Revocation of consent&#xD;
&#xD;
          -  Accommodation in a clinic or similar facility based on an official or judicial order&#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>
  <location>
    <facility>
      <name>University of Hohenheim</name>
      <address>
        <city>Stuttgart</city>
        <zip>70599</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>October 26, 2021</last_update_submitted>
  <last_update_submitted_qc>October 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Hohenheim</investigator_affiliation>
    <investigator_full_name>Stephan C. Bischoff, MD, Professor</investigator_full_name>
    <investigator_title>Professor Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Human Nutrition</keyword>
  <keyword>NCWS</keyword>
  <keyword>Spelt</keyword>
  <keyword>Wheat Bread</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04401956
org study id: ErnMed-Brot
nct id: NCT04401956
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This project aims to verify the hypothesis that spelt products are more tolerable than bread
      wheat products in a target group of individuals with self-diagnosed wheat sensitivity. In
      addition, the influence of different manufacturing processes will be considered.
Wheat cereals are known to be capable of triggering wheat allergy and celiac disease. The
      prevalence of both diseases is about 1%. Recently, another clinical entity was described, the
      non-celiac wheat sensitivity (NCWS). The origin and mechanisms of NCWS are unclear at
      present, but the existence of this new disease entity has been proven by double-blind
      placebo-controlled challenge tests. Three different grain components have been proposed as
      triggers of NCWS, gluten, α-amylase trypsin inhibitors or fermentable carbohydrates
      (FODMAPs).

      It is reported that individuals with self-diagnosed NCWS quite often tolerate spelt products
      much better, even though spelt shows a higher gluten content than bread wheat products.
      Therefore, the question arises whether this putative spelt tolerance can be confirmed on an
      objective basis and whether the underlying molecular mechanisms can be elucidated. So far,
      human study addressing such questions are lacking.

      This project aims to verify the hypothesis that spelt products are more tolerable than bread
      wheat products in a target group of individuals with self-diagnosed wheat sensitivity. In
      addition, the influence of different manufacturing processes on wheat sensitivity will be
      revealed.

      For this purpose, the trial involves individuals with self-diagnosed wheat sensitivity and
      spelt tolerance. Six different kinds of bread will be tested, including 4 wheat and spelt
      breads, each of them produced following a traditional or a conventional way. Aim of this part
      is to objective bread wheat and spelt intolerance in a defined population. To find out
      whether FODMAPs or gluten affect the tolerance of bread, two additional breads will be
      tested, a gluten-free bread with added gluten and a gluten-free bread with added FODMAPs.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: Single (Participant)
measure: Change of IBS-SSS Total score
time frame: Study examinations are at baseline, after wash out phases (day 3, 10, 17, 24, 31, 38) and after bread intervention phases (day 7, 14, 21, 28, 35, 42).)
description: IBS-SSS Total score will be collected with a questionnaire
measure: Extraintestinal Symptoms
time frame: Study examinations are at baseline, after wash out phases (day 3, 10, 17, 24, 31, 38) and after bread intervention phases (day 7, 14, 21, 28, 35, 42).)
description: The study team will ask the participants for typical extraintestinal symptoms in NCWS like headache, foggy-mind, nausea, heartburn, exhaustion
measure: Blood and fecal markers
time frame: Study examinations are at baseline and after bread intervention phases (day 7, 14, 21, 28, 35, 42).
description: Change of blood- and fecal markers that will reveal inflammation or intestinal permeability (Anti-gliadin Immunglobulin G antibody, lipase, ferritin, zonulin, calprotectin and lactoferrin)
arm group label: Gluten free bread with added gluten
arm group type: Active Comparator
description: Bread will be eaten by the participants for 4 consecutive days.
arm group label: Gluten free bread with added FODMAPs
arm group type: Active Comparator
description: Bread will be eaten by the participants for 4 consecutive days.
arm group label: Traditional manufactured wheat bread
arm group type: Experimental
description: Bread will be eaten by the participants for 4 consecutive days.
arm group label: Traditional manufactured spelt bread
arm group type: Experimental
description: Bread will be eaten by the participants for 4 consecutive days.
arm group label: Conventional manufactured wheat bread
arm group type: Experimental
description: Bread will be eaten by the participants for 4 consecutive days.
arm group label: Conventional manufactured spelt bread
arm group type: Experimental
description: Bread will be eaten by the participants for 4 consecutive days.
intervention type: Other
intervention name: bread
description: Different types of bread
arm group label: Conventional manufactured spelt bread
arm group label: Conventional manufactured wheat bread
arm group label: Gluten free bread with added FODMAPs
arm group label: Gluten free bread with added gluten
arm group label: Traditional manufactured spelt bread
arm group label: Traditional manufactured wheat bread
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Hohenheim
investigator full name: Stephan C. Bischoff, MD, Professor
investigator title: Professor Dr. med.
mesh term: Hypersensitivity
sharing ipd: Undecided