<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/NCT04489810</url>
  </required_header>
  <id_info>
    <org_study_id>Project 0470</org_study_id>
    <nct_id>NCT04489810</nct_id>
  </id_info>
  <brief_title>Digestion of Gluten in the Presence of Enzymes</brief_title>
  <acronym>GlutDigest</acronym>
  <official_title>GlutDigest - Enzymes-assisted Gluten Digestion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Deerland Enzymes</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Teagasc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Atlantia Food Clinical Trials</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Deerland Enzymes</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 study evaluates the impact of two dietary supplements (Glutalytic® and DE111®) and of&#xD;
      oatmeal properties on the digestion of gluten and starch and on the glycemic response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RATIONALE Two important factors can influence the proportions of gluten and starch that&#xD;
      resist digestion: (1) enzyme availability and specificity and (2) the structural properties&#xD;
      of the food.&#xD;
&#xD;
      Glutalytic®, is a dietary supplement based on an enzyme preparation which effectively&#xD;
      degrades gluten in vitro (Healey, Hall et al. unpublished). As it has also been found that&#xD;
      the rate of wheat protein digestion can be increased in the presence of amylases (Smith, Pan&#xD;
      et al. 2015), Glutalytic ® is also enriched with amylase to aid in starch digestion.&#xD;
&#xD;
      The structural properties of food are influenced by numerous factors including meal&#xD;
      preparation practices. Two common practices that can influence nutrient availability&#xD;
      differently are heating vs. refrigerating (e.g. oat porridge vs. soaked and refrigerated&#xD;
      oats).&#xD;
&#xD;
      Bacillus subtilis DE111® can produce and secrete many enzymes, including proteases, which, if&#xD;
      secreted into the environment of the digestive tract, could support digestion and, in&#xD;
      particular, the digestion of gluten. However, it is not clear whether diet supplementation&#xD;
      with DE111 is a physiologically viable approach in terms of probiotic survival in the&#xD;
      gastrointestinal tract.&#xD;
&#xD;
      PURPOSE The aims of this study are to better understand the impact of each of these factors&#xD;
      and whether supplementation with probiotic spores is a viable option.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 19, 2020</start_date>
  <completion_date type="Anticipated">April 2021</completion_date>
  <primary_completion_date type="Anticipated">March 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>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Undigested wheat protein</measure>
    <time_frame>9-hour period after the test meal</time_frame>
    <description>Difference between the mean concentration of undigested wheat protein in ileal effluent samples.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vegetative DE111 cells</measure>
    <time_frame>9-hour period after the test meal</time_frame>
    <description>Mean concentration of DE111® cells recovered in the ileal effluent in the vegetative state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycemic response</measure>
    <time_frame>At baseline, and at different time-points during 9 hours after after consuming the test meal.</time_frame>
    <description>Difference between the mean area under the glucose concentration (measured in the interstitial fluid) curves following each treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Undigested starch</measure>
    <time_frame>At baseline and once every hour in the 9-hour period after consumption of the test meal.</time_frame>
    <description>Difference between the mean concentration of undigested starch in ileal effluent samples.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Undigested food particles</measure>
    <time_frame>9-hour period after the test meal</time_frame>
    <description>Pictures of undigested foods particles and microscopy will be combined for a combined assessment of macro- and micro- structural characteristics of the food particles recovered in ileal effluent samples.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Main Focus: Gluten and Starch Digestibility</condition>
  <arm_group>
    <arm_group_label>Meal A + Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>350 mg Placebo capsule, taken by mouth, once, with Meal A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meal A + Glutalytic®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>350 mg Glutalytic® capsule, taken by mouth, once, with Meal A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meal A + DE111®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>350 mg DE111® capsule, taken by mouth, once, with Meal A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meal B + Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>350 mg Placebo capsule, taken by mouth, once, with Meal B</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Maltodextrin capsule manufactured to mimic the Glutalytic® and DE111® capsules</description>
    <arm_group_label>Meal A + Placebo</arm_group_label>
    <arm_group_label>Meal B + Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Glutalytic®</intervention_name>
    <description>1 capsule containing 350 mg of Glutalyltic®</description>
    <arm_group_label>Meal A + Glutalytic®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>DE111®</intervention_name>
    <description>1 capsule containing Bacillus subtilis DE111</description>
    <arm_group_label>Meal A + DE111®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Meal A</intervention_name>
    <description>Oatmeal porridge - serving of cooked oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL</description>
    <arm_group_label>Meal A + DE111®</arm_group_label>
    <arm_group_label>Meal A + Glutalytic®</arm_group_label>
    <arm_group_label>Meal A + Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Meal B</intervention_name>
    <description>Refrigerated oatmeal - serving of refrigerated oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL</description>
    <arm_group_label>Meal B + Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject has given written informed consent&#xD;
&#xD;
          -  Subject has an ileostomy stable for at least 3 months post-operative and shows normal&#xD;
             stoma functions&#xD;
&#xD;
          -  Subject is otherwise healthy&#xD;
&#xD;
          -  Subject is available to participate in the study sessions on the proposed dates&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has coeliac disease or allergy to wheat products and/or any other ingredients&#xD;
             in the test meal and standard meals&#xD;
&#xD;
          -  Case of obstruction of the stoma in the past 3 months&#xD;
&#xD;
          -  Body mass index &lt; 18 kg/m2 or &gt; 30 kg/m2.&#xD;
&#xD;
          -  Diagnosed mouth, throat or active gastrointestinal pathology (other than ileostomy)&#xD;
             that may affect normal ingestion and digestion of food.&#xD;
&#xD;
          -  History of pancreatic disease&#xD;
&#xD;
          -  Subject is immunocompromised (HIV positive, transplant patient, on antirejection&#xD;
             medications, on a steroid for &gt;30 days, or chemotherapy or radiotherapy within the&#xD;
             last year)&#xD;
&#xD;
          -  Subject has Type 1 or Type 2 diabetes mellitus.&#xD;
&#xD;
          -  Subject has a history of bariatric surgery.&#xD;
&#xD;
          -  Subject has a history of drug and/or alcohol abuse at the time of enrolment&#xD;
&#xD;
          -  Subject is currently participating in another study, or plans to participate in&#xD;
             another study during the study period&#xD;
&#xD;
          -  Women of child-bearing potential who do not use an acceptable method of contraception&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Andre Brodkorb, PhD</last_name>
    <phone>+3532542222</phone>
    <email>andre.brodkorb@teagasc.ie</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Daniela Freitas, PhD</last_name>
    <phone>+3532542222</phone>
    <email>daniela.freitas@teagasc.ie</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Atlantia Food Clinical Trials</name>
      <address>
        <city>Cork</city>
        <country>Ireland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+353214307442</phone>
      <email>studies@atlantiafoodtrials.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Ireland</country>
  </location_countries>
  <reference>
    <citation>Smith F, Pan X, Bellido V, Toole GA, Gates FK, Wickham MS, Shewry PR, Bakalis S, Padfield P, Mills EN. Digestibility of gluten proteins is reduced by baking and enhanced by starch digestion. Mol Nutr Food Res. 2015 Oct;59(10):2034-43. doi: 10.1002/mnfr.201500262. Epub 2015 Aug 21.</citation>
    <PMID>26202208</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>February 12, 2021</last_update_submitted>
  <last_update_submitted_qc>February 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gluten</keyword>
  <keyword>Starch</keyword>
  <keyword>Digestive enzymes</keyword>
  <keyword>Probiotics</keyword>
  <patient_data>
    <sharing_ipd>No</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/NCT04489810
org study id: Project 0470
nct id: NCT04489810
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study evaluates the impact of two dietary supplements (Glutalytic® and DE111®) and of
      oatmeal properties on the digestion of gluten and starch and on the glycemic response.
RATIONALE Two important factors can influence the proportions of gluten and starch that
      resist digestion: (1) enzyme availability and specificity and (2) the structural properties
      of the food.

      Glutalytic®, is a dietary supplement based on an enzyme preparation which effectively
      degrades gluten in vitro (Healey, Hall et al. unpublished). As it has also been found that
      the rate of wheat protein digestion can be increased in the presence of amylases (Smith, Pan
      et al. 2015), Glutalytic ® is also enriched with amylase to aid in starch digestion.

      The structural properties of food are influenced by numerous factors including meal
      preparation practices. Two common practices that can influence nutrient availability
      differently are heating vs. refrigerating (e.g. oat porridge vs. soaked and refrigerated
      oats).

      Bacillus subtilis DE111® can produce and secrete many enzymes, including proteases, which, if
      secreted into the environment of the digestive tract, could support digestion and, in
      particular, the digestion of gluten. However, it is not clear whether diet supplementation
      with DE111 is a physiologically viable approach in terms of probiotic survival in the
      gastrointestinal tract.

      PURPOSE The aims of this study are to better understand the impact of each of these factors
      and whether supplementation with probiotic spores is a viable option.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Undigested wheat protein
time frame: 9-hour period after the test meal
description: Difference between the mean concentration of undigested wheat protein in ileal effluent samples.
measure: Vegetative DE111 cells
time frame: 9-hour period after the test meal
description: Mean concentration of DE111® cells recovered in the ileal effluent in the vegetative state.
measure: Glycemic response
time frame: At baseline, and at different time-points during 9 hours after after consuming the test meal.
description: Difference between the mean area under the glucose concentration (measured in the interstitial fluid) curves following each treatment
measure: Undigested starch
time frame: At baseline and once every hour in the 9-hour period after consumption of the test meal.
description: Difference between the mean concentration of undigested starch in ileal effluent samples.
measure: Undigested food particles
time frame: 9-hour period after the test meal
description: Pictures of undigested foods particles and microscopy will be combined for a combined assessment of macro- and micro- structural characteristics of the food particles recovered in ileal effluent samples.
arm group label: Meal A + Placebo
arm group type: Placebo Comparator
description: 350 mg Placebo capsule, taken by mouth, once, with Meal A
arm group label: Meal A + Glutalytic®
arm group type: Experimental
description: 350 mg Glutalytic® capsule, taken by mouth, once, with Meal A
arm group label: Meal A + DE111®
arm group type: Experimental
description: 350 mg DE111® capsule, taken by mouth, once, with Meal A
arm group label: Meal B + Placebo
arm group type: Experimental
description: 350 mg Placebo capsule, taken by mouth, once, with Meal B
intervention type: Dietary Supplement
intervention name: Placebo
description: Maltodextrin capsule manufactured to mimic the Glutalytic® and DE111® capsules
arm group label: Meal A + Placebo
arm group label: Meal B + Placebo
intervention type: Dietary Supplement
intervention name: Glutalytic®
description: 1 capsule containing 350 mg of Glutalyltic®
arm group label: Meal A + Glutalytic®
intervention type: Dietary Supplement
intervention name: DE111®
description: 1 capsule containing Bacillus subtilis DE111
arm group label: Meal A + DE111®
intervention type: Other
intervention name: Meal A
description: Oatmeal porridge - serving of cooked oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL
arm group label: Meal A + DE111®
arm group label: Meal A + Glutalytic®
arm group label: Meal A + Placebo
intervention type: Other
intervention name: Meal B
description: Refrigerated oatmeal - serving of refrigerated oats containing 50g of carbohydrates (excluding sugars); Wheat cereal - serving of wheat cereal providing 1g of gluten; Water - 125 mL
arm group label: Meal B + Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andre Brodkorb, PhD
phone: +3532542222
email: andre.brodkorb@teagasc.ie
last name: Daniela Freitas, PhD
phone: +3532542222
email: daniela.freitas@teagasc.ie
facility: 
status: Recruiting
contact: 
country: Ireland
citation: Smith F, Pan X, Bellido V, Toole GA, Gates FK, Wickham MS, Shewry PR, Bakalis S, Padfield P, Mills EN. Digestibility of gluten proteins is reduced by baking and enhanced by starch digestion. Mol Nutr Food Res. 2015 Oct;59(10):2034-43. doi: 10.1002/mnfr.201500262. Epub 2015 Aug 21.
PMID: 26202208
responsible party type: Sponsor
sharing ipd: No