<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/NCT03271138</url>
  </required_header>
  <id_info>
    <org_study_id>GlobalIP</org_study_id>
    <secondary_id>001</secondary_id>
    <nct_id>NCT03271138</nct_id>
  </id_info>
  <brief_title>Bifidobacterium Infantis NLS Super Strain for Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms</brief_title>
  <official_title>A Randomized Controlled Trial of Dietary Supplementation With Bifidobacterium Infantis NLS Super Strain Among Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Global Institute of Probiotics</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dr. C. Bonorino Udaondo Gastroenterology Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Institute, Universidad del Salvador</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Consejo de Investigaciones en Salud, Ministerio de Salud, Gobierno Autónomo de Buenos Aires</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Global Institute of Probiotics</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 primary purpose of this randomized, double-blinded, placebo-controlled, crossover&#xD;
      clinical trial is to evaluate the efficacy of dietary supplementation with Bifidobacterium&#xD;
      infantis NLS super strain among celiac disease patients on a gluten-free who have persistent&#xD;
      gastrointestinal symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Most patients with celiac disease demonstrate substantial clinical improvement during the&#xD;
      first few weeks after the onset of the consumption of a gluten-free diet. However, between&#xD;
      30-50% of patients with celiac disease have persistent gastrointestinal symptoms despite&#xD;
      consuming a gluten-free diet and presenting negative antibodies. It has recently been&#xD;
      reported that celiac disease patients treated with a gluten-free diet that still have&#xD;
      persistent symptoms possess different intestinal microbiota patterns than patients without&#xD;
      persistent symptoms. Furthermore, a pilot study showed that dietary supplementation with&#xD;
      probiotics (Bifidobacterium infantis NLS super strain - Natren LIFESTART®) in untreated&#xD;
      celiac disease patients was associated with a significant improvement in symptoms as compared&#xD;
      to placebo. Collectively, these findings contribute to the hypothesis that celiac disease&#xD;
      patients on a gluten-free diet in whom gastrointestinal symptoms persist may benefit from the&#xD;
      supplementation of Bifidobacterium infantis NLS super strain.&#xD;
&#xD;
      Participants in this double-blinded crossover trial will be randomized to receive either&#xD;
      placebo or Bifidobacterium infantis NLS super strain for 3 weeks, followed by a 2 week&#xD;
      washout period, and then followed by 3 weeks of the other of either placebo or probiotic&#xD;
      supplementation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 21, 2017</start_date>
  <completion_date type="Actual">December 7, 2017</completion_date>
  <primary_completion_date type="Actual">December 7, 2017</primary_completion_date>
  <phase>Phase 2</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>Changes in Gastrointestinal Symptom Rating Scale (GSRS)</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Celiac Symptoms Index (CSI)</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Quality of Life: SF-36</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gut microbiota</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
    <description>16S rRNA Illumina based sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Gluten Immunogenic Peptides (GIP)</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in serology (IgA tTG &amp; IgA DGP)</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in anthropometric measurements (BMI)</measure>
    <time_frame>Baseline, End of Period I (3 weeks), End of Period II (8 weeks)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Celiac Disease</condition>
  <arm_group>
    <arm_group_label>Bifidobacterium Infantis NLS Super Strain</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in the probiotic period will take two capsules of Bifidobacterium infantis NLS super strain (Natren LIFE START®2) three times per day for three weeks. Each capsule contains 2 x 10^9 colony-forming units (CFU) of Bifidobacterium infantis NLS super strain, for a total daily dose of 12 X 10^9 CFU. The probiotic will be kept refrigerated during transportation and throughout the study period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants in the placebo period will take two capsules of placebo three times per day for three weeks. The placebo capsules contain rice flour, hydroxypropyl and methylcellulose. The placebo will be kept refrigerated during transportation and throughout the study period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Bifidobacterium infantis NLS super strain (Natren LIFE START®2)</intervention_name>
    <description>2 capsules, 3 times per day, for daily total of 12x10^9 CFU Bifidobacterium infantis NLS super strain</description>
    <arm_group_label>Bifidobacterium Infantis NLS Super Strain</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 capsules, 3 times per day, containing rice flour, hydroxypropyl and methylcellulose</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women at least 18 years of age&#xD;
&#xD;
          -  Precise diagnosis of celiac disease: serology (a-tTG IgA and/or DGP IgG and/or EmA)&#xD;
             and histology (Marsh IIIa or greater) concordantly positive, confirmed at&#xD;
             investigator's institution&#xD;
&#xD;
          -  Consuming a gluten-free diet for at least 2 years&#xD;
&#xD;
          -  Persistent gastrointestinal symptoms: global GSRS questionnaires ≥2 or ≥ 3 points for&#xD;
             any of the 5 sub-dimensions&#xD;
&#xD;
          -  Signature of informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients not interested or unable to comply with questionnaires and collection of&#xD;
             samples of blood, feces, and urine&#xD;
&#xD;
          -  Complicated celiac disease (refractory, ulcerative jejunoileitis, lymphoma)&#xD;
&#xD;
          -  Concomitant pathologies that are uncompensated or untreated (Type I or II diabetes&#xD;
             mellitus, hyperthyroidism, hypothyroidism, diarrhea due to bile salts, pancreatic&#xD;
             insufficiency, bacterial overgrowth)&#xD;
&#xD;
          -  Consumption within the 2 weeks prior to study enrollment of medication that interferes&#xD;
             with bowel functioning (antibiotics, NSAIDs, laxatives, metformin, opiates,&#xD;
             anticholinergics [atropine, antidepressants, neuroleptics, antipsychotics,&#xD;
             antiparkinsonians], anticonvulsants, antihistamines, antihypertensives [calcium&#xD;
             antagonists, clonidine, diuretics, metal ions (aluminum), antacids, sucralfate, barium&#xD;
             sulfate, bismuth, calcium, iron, heavy metals (arsenic, lead, mercury)], resins&#xD;
             (cholestyramine), or any other medication deemed relevant by the investigator).&#xD;
&#xD;
          -  Women that are pregnant or may become pregnant during the study&#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>Edgardo Smecuol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dr. C. Bonorino Udaondo Gastroenterology Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julio C Bai, MD</last_name>
    <role>Study Director</role>
    <affiliation>Dr. C. Bonorino Udaondo Gastroenterology Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Small Bowel Section, Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 30, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <last_update_submitted>August 23, 2018</last_update_submitted>
  <last_update_submitted_qc>August 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Celiac Disease</keyword>
  <keyword>Gluten-Free Diet</keyword>
  <keyword>Bifidobacterium infantis NLS super strain</keyword>
  <keyword>gastrointestinal symptoms</keyword>
  <keyword>quality of life</keyword>
  <keyword>microbiota</keyword>
  <keyword>IgA TTG</keyword>
  <keyword>IgA DGP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Celiac Disease</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/NCT03271138
org study id: GlobalIP
secondary id: 001
nct id: NCT03271138
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary purpose of this randomized, double-blinded, placebo-controlled, crossover
      clinical trial is to evaluate the efficacy of dietary supplementation with Bifidobacterium
      infantis NLS super strain among celiac disease patients on a gluten-free who have persistent
      gastrointestinal symptoms.
Most patients with celiac disease demonstrate substantial clinical improvement during the
      first few weeks after the onset of the consumption of a gluten-free diet. However, between
      30-50% of patients with celiac disease have persistent gastrointestinal symptoms despite
      consuming a gluten-free diet and presenting negative antibodies. It has recently been
      reported that celiac disease patients treated with a gluten-free diet that still have
      persistent symptoms possess different intestinal microbiota patterns than patients without
      persistent symptoms. Furthermore, a pilot study showed that dietary supplementation with
      probiotics (Bifidobacterium infantis NLS super strain - Natren LIFESTART®) in untreated
      celiac disease patients was associated with a significant improvement in symptoms as compared
      to placebo. Collectively, these findings contribute to the hypothesis that celiac disease
      patients on a gluten-free diet in whom gastrointestinal symptoms persist may benefit from the
      supplementation of Bifidobacterium infantis NLS super strain.

      Participants in this double-blinded crossover trial will be randomized to receive either
      placebo or Bifidobacterium infantis NLS super strain for 3 weeks, followed by a 2 week
      washout period, and then followed by 3 weeks of the other of either placebo or probiotic
      supplementation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in Gastrointestinal Symptom Rating Scale (GSRS)
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
measure: Changes in Celiac Symptoms Index (CSI)
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
measure: Changes in Quality of Life: SF-36
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
measure: Changes in gut microbiota
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
description: 16S rRNA Illumina based sequencing
measure: Changes in Gluten Immunogenic Peptides (GIP)
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
measure: Changes in serology (IgA tTG & IgA DGP)
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
measure: Changes in anthropometric measurements (BMI)
time frame: Baseline, End of Period I (3 weeks), End of Period II (8 weeks)
arm group label: Bifidobacterium Infantis NLS Super Strain
arm group type: Active Comparator
description: Participants in the probiotic period will take two capsules of Bifidobacterium infantis NLS super strain (Natren LIFE START®2) three times per day for three weeks. Each capsule contains 2 x 10^9 colony-forming units (CFU) of Bifidobacterium infantis NLS super strain, for a total daily dose of 12 X 10^9 CFU. The probiotic will be kept refrigerated during transportation and throughout the study period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants in the placebo period will take two capsules of placebo three times per day for three weeks. The placebo capsules contain rice flour, hydroxypropyl and methylcellulose. The placebo will be kept refrigerated during transportation and throughout the study period.
intervention type: Dietary Supplement
intervention name: Bifidobacterium infantis NLS super strain (Natren LIFE START®2)
description: 2 capsules, 3 times per day, for daily total of 12x10^9 CFU Bifidobacterium infantis NLS super strain
arm group label: Bifidobacterium Infantis NLS Super Strain
intervention type: Other
intervention name: Placebo
description: 2 capsules, 3 times per day, containing rice flour, hydroxypropyl and methylcellulose
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edgardo Smecuol, MD
role: Principal Investigator
affiliation: Dr. C. Bonorino Udaondo Gastroenterology Hospital
last name: Julio C Bai, MD
role: Study Director
affiliation: Dr. C. Bonorino Udaondo Gastroenterology Hospital
facility: 
country: Argentina
responsible party type: Sponsor
mesh term: Celiac Disease