<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/NCT03775499</url>
  </required_header>
  <id_info>
    <org_study_id>17.11.NRC</org_study_id>
    <nct_id>NCT03775499</nct_id>
  </id_info>
  <brief_title>Probiotic BL NCC 2705 and Gluten Sensitivity</brief_title>
  <official_title>Proof of Concept Clinical Trial of Safety and Biological Activity of Bifidobacterium Longum NCC 2705 in Gluten Sensitivity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Société des Produits Nestlé (SPN)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Société des Produits Nestlé (SPN)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to confirm/prove safety of the probiotic and production of serpin in&#xD;
      humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial is a multicenter, double blind, randomized, placebo controlled, 2 by 2 cross-over&#xD;
      design (i.e. 2-sequences, 2-periods, 2-treatments) for each specific population (i.e.&#xD;
      self-reported Non Coeliac Gluten Sensitivity and Coeliac Disease subjects).&#xD;
&#xD;
      1 capsule of BL NCC 2705 or placebo will be given twice a day in the morning and in the&#xD;
      evening with a meal over 2 periods of 4 days.&#xD;
&#xD;
      On day four a single dose of gluten (3g) will be administered and duodenal fluid will be&#xD;
      collected in the following hours through a naso-intestinal catheter. The viability of BL NCC&#xD;
      2705, the production of serpin and its effects on gluten digestion and intestinal enzymatic&#xD;
      activity will be determined.&#xD;
&#xD;
      No chronic administration of gluten as a challenge is foreseen in the study.&#xD;
&#xD;
      After a wash out period of minimum 2 weeks, period will be repeated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 9, 2018</start_date>
  <completion_date type="Actual">December 15, 2020</completion_date>
  <primary_completion_date type="Actual">October 4, 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>incidence, type and severity of adverse event</measure>
    <time_frame>from Baseline to end of study (up to maximum 43 days)</time_frame>
    <description>incidence, type and severity of adverse event</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gastro-intestinal tolerability: visual analog scale</measure>
    <time_frame>from Baseline to end of study (up to maximum 43 days)</time_frame>
    <description>Sum of visual analog scale for gastro-intestinal symptoms assessment (nausea, vomiting, diarrhea, audible bowel sound, flatulence and abdominal cramping symptoms are assessed). Each scale is from 0 (no symptom) to 100mm (maximum symptom). The maximum sum value is 600.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentration of bacterial Serpin RNA and/or proteins (ng/mL) in duodenal aspirates</measure>
    <time_frame>19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)</time_frame>
    <description>Measurements via RT-PRC and immuno-assay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Probiotic BL NCC 2705 (ng/mL) in duodenal aspirates</measure>
    <time_frame>19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)</time_frame>
    <description>Measurements via PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of gluten derived pepides in duodenal aspirates</measure>
    <time_frame>10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36)</time_frame>
    <description>Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in duodenal apsirates</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of gluten derived pepides in urine</measure>
    <time_frame>10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36)</time_frame>
    <description>Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in urine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of elastase (Units/ mL) activity in duodenal aspirates</measure>
    <time_frame>19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)</time_frame>
    <description>Measurements of proteolytic activity based assay</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Celiac Disease</condition>
  <condition>Non-celiac Gluten Sensitivity</condition>
  <arm_group>
    <arm_group_label>Period 1: Placebo - Period 2: BL NCC 2705</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Period 1: BL NCC 2705 - Period 2: Placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Intervention 1 : BL NCC 2705 + Maltodextrin</intervention_name>
    <description>2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day</description>
    <arm_group_label>Period 1: BL NCC 2705 - Period 2: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intervention 1 : Maltodextrin</intervention_name>
    <description>2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day</description>
    <arm_group_label>Period 1: Placebo - Period 2: BL NCC 2705</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Intervention 2 : BL NCC 2705 + Maltodextrin</intervention_name>
    <description>2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day</description>
    <arm_group_label>Period 1: Placebo - Period 2: BL NCC 2705</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Intervention 2 : Maltodextrin</intervention_name>
    <description>2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day</description>
    <arm_group_label>Period 1: BL NCC 2705 - Period 2: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to sign written informed consent prior to trial entry&#xD;
&#xD;
          2. Male or female adults &gt;18 years of age&#xD;
&#xD;
          3. For NCGS: self-reported gluten sensitivity with negative CD serology, on gluten free&#xD;
             diet for at least 6 weeks with self-reported significant symptomatic improvement&#xD;
&#xD;
          4. For CD: confirmed serologic and histologic diagnosis of CD and on GFD for at least 12&#xD;
             months with self-reported significant symptomatic improvement&#xD;
&#xD;
          5. Body Mass Index (BMI) within the range &gt;18 - &lt;30 kg/m2&#xD;
&#xD;
          6. Willing and able to comply with study procedures and restrictions&#xD;
&#xD;
          7. In good health as determined by a medical history and medical examination&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Documented IgE-mediated food allergy&#xD;
&#xD;
          2. Subjects following an overly imbalanced or restrictive diet as per nutritional advice&#xD;
&#xD;
          3. Concurrent systemic disease and/or laboratory abnormalities considered by&#xD;
             investigators to be detrimental for the participants safety or potentially interfering&#xD;
             with the study procedures and/or study outcomes&#xD;
&#xD;
          4. Concurrent organic GI pathology other than benign polyps, diverticulosis, hemorrhoids,&#xD;
             lipomas and melanosis coli&#xD;
&#xD;
          5. Previous abdominal surgery with the exception of hernia repair, appendectomy,&#xD;
             caesarian section, tubal ligation, hysterectomy, hemorrhoidectomy&#xD;
&#xD;
          6. Patients who received antibiotics in the previous 2 weeks&#xD;
&#xD;
          7. women of childbearing potential not willing to use an effective contraception method&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carmine D'Urzo, Dr.</last_name>
    <role>Study Director</role>
    <affiliation>Nestec Ltd.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Viecuri Hospital</name>
      <address>
        <city>Venlo</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 1, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>December 22, 2020</last_update_submitted>
  <last_update_submitted_qc>December 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiac Disease</mesh_term>
    <mesh_term>Hypersensitivity</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/NCT03775499
org study id: 17.11.NRC
nct id: NCT03775499
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim of the study is to confirm/prove safety of the probiotic and production of serpin in
      humans.
This trial is a multicenter, double blind, randomized, placebo controlled, 2 by 2 cross-over
      design (i.e. 2-sequences, 2-periods, 2-treatments) for each specific population (i.e.
      self-reported Non Coeliac Gluten Sensitivity and Coeliac Disease subjects).

      1 capsule of BL NCC 2705 or placebo will be given twice a day in the morning and in the
      evening with a meal over 2 periods of 4 days.

      On day four a single dose of gluten (3g) will be administered and duodenal fluid will be
      collected in the following hours through a naso-intestinal catheter. The viability of BL NCC
      2705, the production of serpin and its effects on gluten digestion and intestinal enzymatic
      activity will be determined.

      No chronic administration of gluten as a challenge is foreseen in the study.

      After a wash out period of minimum 2 weeks, period will be repeated.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: incidence, type and severity of adverse event
time frame: from Baseline to end of study (up to maximum 43 days)
description: incidence, type and severity of adverse event
measure: Gastro-intestinal tolerability: visual analog scale
time frame: from Baseline to end of study (up to maximum 43 days)
description: Sum of visual analog scale for gastro-intestinal symptoms assessment (nausea, vomiting, diarrhea, audible bowel sound, flatulence and abdominal cramping symptoms are assessed). Each scale is from 0 (no symptom) to 100mm (maximum symptom). The maximum sum value is 600.
measure: Concentration of bacterial Serpin RNA and/or proteins (ng/mL) in duodenal aspirates
time frame: 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)
description: Measurements via RT-PRC and immuno-assay
measure: Concentration of Probiotic BL NCC 2705 (ng/mL) in duodenal aspirates
time frame: 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)
description: Measurements via PCR
measure: Concentration of gluten derived pepides in duodenal aspirates
time frame: 10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36)
description: Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in duodenal apsirates
measure: Concentration of gluten derived pepides in urine
time frame: 10 sampling over 3h30 at visit 2 (day 4) and visit 3 (from day 22 to day 36)
description: Effect of BL NCC 2705 on gluten digestion based on the amount of gluten peptides detected in urine
measure: Level of elastase (Units/ mL) activity in duodenal aspirates
time frame: 19 sampling over 6h50 hours at visit 2 (day 4) and visit 3 (from day 22 to day 36)
description: Measurements of proteolytic activity based assay
arm group label: Period 1: Placebo - Period 2: BL NCC 2705
arm group type: Other
description: For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)
arm group label: Period 1: BL NCC 2705 - Period 2: Placebo
arm group type: Other
description: For the 2 populations (Celiac and Non-Celiac Gluten Sensitivity)
intervention type: Dietary Supplement
intervention name: Intervention 1 : BL NCC 2705 + Maltodextrin
description: 2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day
arm group label: Period 1: BL NCC 2705 - Period 2: Placebo
intervention type: Other
intervention name: Intervention 1 : Maltodextrin
description: 2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day
arm group label: Period 1: Placebo - Period 2: BL NCC 2705
intervention type: Dietary Supplement
intervention name: Intervention 2 : BL NCC 2705 + Maltodextrin
description: 2 capsules of BL NCC 2705/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of BL NCC 2705 in the morning of the 4th day
arm group label: Period 1: Placebo - Period 2: BL NCC 2705
intervention type: Other
intervention name: Intervention 2 : Maltodextrin
description: 2 capsules of Placebo/day (1 in the morning and 1 in the evening) for 3 days + 1 capsule of Placebo in the morning of the 4th day
arm group label: Period 1: BL NCC 2705 - Period 2: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Carmine D'Urzo, Dr.
role: Study Director
affiliation: Nestec Ltd.
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Celiac Disease
mesh term: Hypersensitivity