<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/NCT03301103</url>
  </required_header>
  <id_info>
    <org_study_id>NL62453.028.17</org_study_id>
    <nct_id>NCT03301103</nct_id>
  </id_info>
  <brief_title>PTM202 and Modulation of Host Resistance to Diarrheagenic E. Coli</brief_title>
  <acronym>APA12/PANTER</acronym>
  <official_title>PTM202 and Modulation of Host Resistance to Diarrheagenic Escherichia Coli in a Randomized, Double-blind, Placebo Controlled Study in Healthy Human Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NIZO Food Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>PanTheryx, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NIZO Food Research</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The APA12/PANTER study is a parallel 3-weeks intervention study. Subjects will be randomly&#xD;
      assigned to one of two treatment groups; placebo or PTM202 (n=36 per group). After an&#xD;
      overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic&#xD;
      E. coli at study day 14. At various time points before and after diarrheagenic E. coli&#xD;
      challenge an online diary will be kept to record information on stool consistency, frequency&#xD;
      and severity of symptoms and stool samples will be collected to determine total fecal wet&#xD;
      weight and percentage of fecal wet weight.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The APA12/PANTER study is a randomized, double-blind, placebo-controlled, parallel&#xD;
      intervention study of 3 weeks in 72 healthy adults. The study will include 2 arms; PTM202 and&#xD;
      placebo. Subjects will be instructed to maintain their usual pattern of physical activity and&#xD;
      their habitual food intake, but to standardize their dietary calcium intake. After an&#xD;
      overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic&#xD;
      E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).&#xD;
&#xD;
      At study day 14, 15 and 16 subjects will receive either placebo or PTM202, a dietary formula&#xD;
      containing dried bovine colostrum and dried whole egg.&#xD;
&#xD;
      Before and after the diarrheagenic E. coli challenge an online diary will be kept to record&#xD;
      information on stool consistency, frequency, severity of symptoms and mediation intake. At&#xD;
      various time points before and after diarrheagenic E. coli challenge stool samples will be&#xD;
      collected. The main study parameters are Stool consistency (Bristol Stool Scale reported by&#xD;
      the subjects in the online diary, and Percentage of fecal wet weight (% determined by&#xD;
      freeze-drying).&#xD;
&#xD;
      Secondary study parameters are: Stool frequency (Stools per day reported by the subjects in&#xD;
      the online diary), Total fecal wet weight (fecal weight in g/day), and the incidence and&#xD;
      severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by&#xD;
      the subjects in the online diary).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 7, 2017</start_date>
  <completion_date type="Actual">March 16, 2018</completion_date>
  <primary_completion_date type="Actual">January 23, 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>Parallel Assignment</intervention_model>
    <intervention_model_description>The APA12/PANTER study is a randomized, double-blind, placebo-controlled, parallel intervention study of 3 weeks in 72 healthy adults. Subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14). At study day 14, 15 and 16 subjects will receive either placebo or PTM202, a dietary formula containing dried bovine colostrum and dried whole egg.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>All researchers of the project team will be kept blind to assignment of treatment, and so will be the study subjects.The placebo will be matched in appearance and flavour to PTM202.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Stool consistency</measure>
    <time_frame>Before challenge (Day 11-13), After challenge (Day 14-18)</time_frame>
    <description>Change in stool consistency score (questionnaire) before and after E. coli challenge</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Relative fecal wet weight</measure>
    <time_frame>Before challenge (Day 11-13), After challenge (Day 14-18)</time_frame>
    <description>Change in relative fecal wet weight (freeze-drying) before and after E. coli challenge</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stool frequency</measure>
    <time_frame>Before challenge (Day 11-13), After challenge (Day 14-18)</time_frame>
    <description>Change in stool frequency (questionnaire) before and after E. coli challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total fecal wet weight</measure>
    <time_frame>Before challenge (Day 11-13), After challenge (Day 14-18)</time_frame>
    <description>Change in total fecal wet weight (wet weight measurement) before and after E. coli challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastro-intestinal symptoms</measure>
    <time_frame>Before challenge (Day 11-13), After challenge (Day 14-18)</time_frame>
    <description>Change in gastro-intestinal symptoms (questionnaire) before and after E. coli challenge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">72</enrollment>
  <condition>Traveler's Diarrhea</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo will consist of low-lactose isonitrogenous soy product, and will be matched in appearance and flavour to PTM202.&#xD;
After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PTM202</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PTM202 is a dry powder for reconstitution, comprised of a proprietary mixture of dried bovine colostrum and dried whole egg.&#xD;
After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>E. coli strain E1392-75-2A</intervention_name>
    <description>After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).</description>
    <arm_group_label>PTM202</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PTM202</intervention_name>
    <description>PTM202 is a dietary formula containing a proprietary mixture of dried bovine colostrum and dried whole egg.</description>
    <arm_group_label>PTM202</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male;&#xD;
&#xD;
          2. Age between 18 and 55 years;&#xD;
&#xD;
          3. BMI ≥18 and ≤27 kg/m2;&#xD;
&#xD;
          4. Healthy as assessed by the NIZO food research medical questionnaire.&#xD;
&#xD;
          5. Ability to follow verbal and written instructions;&#xD;
&#xD;
          6. Availability of internet connection;&#xD;
&#xD;
          7. Signed informed consent;&#xD;
&#xD;
          8. Willing to accept disclosure of the financial benefit of participation in the study to&#xD;
             the authorities concerned;&#xD;
&#xD;
          9. Willing to accept use of all encoded data, including publication, and the confidential&#xD;
             use and storage of all data for at least 15 years;&#xD;
&#xD;
         10. Willing to comply with study procedures, including collection of stool samples;&#xD;
&#xD;
         11. Willingness to abstain from high calcium containing products;&#xD;
&#xD;
         12. Willingness to abstain from alcoholic beverages three days before, during and for four&#xD;
             days after diarrheagenic E. coli challenge;&#xD;
&#xD;
         13. Willingness to abstain from antibiotics, norit, laxatives, nonsteroidal&#xD;
             anti-inflammatory drugs (OTC), opiates, antacids, proton pump inhibitors, and&#xD;
             antimotility agents (e.g., loperamide) on the three days before, during and for four&#xD;
             days after diarrheagenic E. coli challenge.&#xD;
&#xD;
         14. Willingness to abstain from probiotics three days before, during and for four days&#xD;
             after diarrheagenic E. coli challenge;&#xD;
&#xD;
         15. Willingness to give up blood donation starting 1 month prior to study start and during&#xD;
             the entire study;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any confirmed or suspected immunosuppressive or immunodeficient condition including&#xD;
             human immunodeficiency virus infection (HIV);&#xD;
&#xD;
          2. Disease of the GI tract, liver, bile bladder, kidney, thyroid gland (self-reported);&#xD;
&#xD;
          3. Diarrheagenic E. coli strain (as used in the study) detected in fecal sample at&#xD;
             screening;&#xD;
&#xD;
          4. Evidence of current excessive alcohol consumption or non-therapeutic drug (ab)use);&#xD;
&#xD;
          5. High titer serum antibodies against CFA-II diarrheagenic E. coli strain (as used in&#xD;
             the study) at screening;&#xD;
&#xD;
          6. History of microbiologically confirmed ETEC or cholera infection in last 3 years;&#xD;
&#xD;
          7. Known allergy to the following antibiotics: ciprofloxacin,&#xD;
             trimethoprim-sulfamethoxazole, and penicillins;&#xD;
&#xD;
          8. Known allergy to soy, milk- and/or egg;&#xD;
&#xD;
          9. Mental status that is incompatible with the proper conduct of the study;&#xD;
&#xD;
         10. Occupation involving handling of ETEC or Vibrio cholerae currently, or in the past 3&#xD;
             years;&#xD;
&#xD;
         11. Reported average stool frequency of &lt;1 or &gt;3 per day;&#xD;
&#xD;
         12. Symptoms consistent with Travelers' Diarrhea concurrent with travel to countries where&#xD;
             ETEC infection is endemic (most of the developing world) within 3 years prior to&#xD;
             dosing, OR planned travel to endemic countries during the length of the study;&#xD;
&#xD;
         13. Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion),&#xD;
             cholesterol lowering agents, antacids, proton pump inhibitors and immune suppressive&#xD;
             agents (up till 3 months prior to inclusion);&#xD;
&#xD;
         14. Vaccination for or ingestion of ETEC, cholera, or E coli heat labile toxin within 3&#xD;
             years prior to inclusion;&#xD;
&#xD;
         15. Vegans.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Gender identity is self-reported by the subjects through a questionnaire.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Van Schaik</last_name>
    <role>Study Director</role>
    <affiliation>NIZO Food Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NIZO</name>
      <address>
        <city>Ede</city>
        <state>Gelderland</state>
        <zip>6718ZB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>July 17, 2018</last_update_submitted>
  <last_update_submitted_qc>July 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nutrition</keyword>
  <keyword>Gastroenteritis</keyword>
  <keyword>Traveler's diarrhea</keyword>
  <keyword>E. coli</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <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/NCT03301103
org study id: NL62453.028.17
nct id: NCT03301103
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The APA12/PANTER study is a parallel 3-weeks intervention study. Subjects will be randomly
      assigned to one of two treatment groups; placebo or PTM202 (n=36 per group). After an
      overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic
      E. coli at study day 14. At various time points before and after diarrheagenic E. coli
      challenge an online diary will be kept to record information on stool consistency, frequency
      and severity of symptoms and stool samples will be collected to determine total fecal wet
      weight and percentage of fecal wet weight.
The APA12/PANTER study is a randomized, double-blind, placebo-controlled, parallel
      intervention study of 3 weeks in 72 healthy adults. The study will include 2 arms; PTM202 and
      placebo. Subjects will be instructed to maintain their usual pattern of physical activity and
      their habitual food intake, but to standardize their dietary calcium intake. After an
      overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic
      E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).

      At study day 14, 15 and 16 subjects will receive either placebo or PTM202, a dietary formula
      containing dried bovine colostrum and dried whole egg.

      Before and after the diarrheagenic E. coli challenge an online diary will be kept to record
      information on stool consistency, frequency, severity of symptoms and mediation intake. At
      various time points before and after diarrheagenic E. coli challenge stool samples will be
      collected. The main study parameters are Stool consistency (Bristol Stool Scale reported by
      the subjects in the online diary, and Percentage of fecal wet weight (% determined by
      freeze-drying).

      Secondary study parameters are: Stool frequency (Stools per day reported by the subjects in
      the online diary), Total fecal wet weight (fecal weight in g/day), and the incidence and
      severity of Gastro-intestinal symptoms (Gastro-intestinal Symptom Rating Scale reported by
      the subjects in the online diary).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The APA12/PANTER study is a randomized, double-blind, placebo-controlled, parallel intervention study of 3 weeks in 72 healthy adults. Subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14). At study day 14, 15 and 16 subjects will receive either placebo or PTM202, a dietary formula containing dried bovine colostrum and dried whole egg.
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: All researchers of the project team will be kept blind to assignment of treatment, and so will be the study subjects.The placebo will be matched in appearance and flavour to PTM202.
measure: Stool consistency
time frame: Before challenge (Day 11-13), After challenge (Day 14-18)
description: Change in stool consistency score (questionnaire) before and after E. coli challenge
measure: Relative fecal wet weight
time frame: Before challenge (Day 11-13), After challenge (Day 14-18)
description: Change in relative fecal wet weight (freeze-drying) before and after E. coli challenge
measure: Stool frequency
time frame: Before challenge (Day 11-13), After challenge (Day 14-18)
description: Change in stool frequency (questionnaire) before and after E. coli challenge
measure: Total fecal wet weight
time frame: Before challenge (Day 11-13), After challenge (Day 14-18)
description: Change in total fecal wet weight (wet weight measurement) before and after E. coli challenge
measure: Gastro-intestinal symptoms
time frame: Before challenge (Day 11-13), After challenge (Day 14-18)
description: Change in gastro-intestinal symptoms (questionnaire) before and after E. coli challenge
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo will consist of low-lactose isonitrogenous soy product, and will be matched in appearance and flavour to PTM202.
After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).
arm group label: PTM202
arm group type: Experimental
description: PTM202 is a dry powder for reconstitution, comprised of a proprietary mixture of dried bovine colostrum and dried whole egg.
After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).
intervention type: Biological
intervention name: E. coli strain E1392-75-2A
description: After an overnight fast, subjects will be orally infected with a live, but attenuated, diarrheagenic E. coli (strain E1392-75-2A; collection NIZO food research; dose 1E10 CFU (at study day 14).
arm group label: PTM202
arm group label: Placebo
intervention type: Device
intervention name: PTM202
description: PTM202 is a dietary formula containing a proprietary mixture of dried bovine colostrum and dried whole egg.
arm group label: PTM202
criteria: 
gender: Male
gender based: Yes
gender description: Gender identity is self-reported by the subjects through a questionnaire.
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Van Schaik
role: Study Director
affiliation: NIZO Food Research
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Diarrhea
sharing ipd: No