<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/NCT02238548</url>
  </required_header>
  <id_info>
    <org_study_id>NL49042.081.14</org_study_id>
    <nct_id>NCT02238548</nct_id>
  </id_info>
  <brief_title>Effect of Raw Milk on the Immune Response Upon Cholera Vaccination</brief_title>
  <acronym>MOSAIC</acronym>
  <official_title>Effect of Raw Milk on the Immune Response Upon Cholera Vaccination</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NIZO Food Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FrieslandCampina</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NIZO Food Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Rationale: Infections are an important worldwide cause of death, both in elderly and young&#xD;
      children. Therefore, support of immunity could help to reduce the incidence of infections. To&#xD;
      screen the potential of specific foods or food ingredients to support immunity, oral&#xD;
      vaccination can serve as a model. In this study, oral cholera vaccination will be applied in&#xD;
      human adult volunteers, and used as a model to study the support of the immune response by&#xD;
      raw milk.&#xD;
&#xD;
      Objective: To investigate whether raw milk is able to enhance the immune response as induced&#xD;
      by oral cholera vaccination.&#xD;
&#xD;
      Study design: The study is designed as a single-blind randomized controlled trial of 4 weeks.&#xD;
&#xD;
      Study population: Healthy subjects of 18-50 years of age.&#xD;
&#xD;
      Intervention: Raw milk, obtained from farms that comply to the high quality requirements for&#xD;
      production of raw milk, and that has been screened according to the safety criteria for raw&#xD;
      milk.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2016</completion_date>
  <primary_completion_date type="Actual">November 2014</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cholera toxin-specific IgA and IgG antibody level in nasal wash as a marker of the vaccination response</measure>
    <time_frame>baseline and day 18</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the cholera toxin-specific IgA and IgG antibody level in serum as a marker of the vaccination response</measure>
    <time_frame>baseline and day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the cholera toxin-specific IgA antibody level in feces as a marker of the vaccination response</measure>
    <time_frame>baseline and day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the cholera toxin-specific IgA and IgG antibody level in saliva as a marker of the vaccination response</measure>
    <time_frame>baseline and day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the expression of tissue homing markers on IgA and IgG antibody-secreting B cells in peripheral blood as markers of the route of modulation of the vaccination response</measure>
    <time_frame>baseline and day 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cholera toxin-specific T cell proliferation as marker of modulation of the vaccination response</measure>
    <time_frame>baseline and day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Infection</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Regular cholera vaccination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Milk bolus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cholera vaccination - raw milk - bolus</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Milk controlled</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cholera vaccination - raw milk - controlled intake</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cholera vaccination</intervention_name>
    <description>Oral cholera vaccination on day 0 and day 14</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Milk bolus</arm_group_label>
    <arm_group_label>Milk controlled</arm_group_label>
    <other_name>Dukoral</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Raw milk</intervention_name>
    <arm_group_label>Milk bolus</arm_group_label>
    <arm_group_label>Milk controlled</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-50 yr&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Availability of internet connection&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Willing to stop blood donation at the blood bank during the study period&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently participating in another clinical trial&#xD;
&#xD;
          -  Previous Cholera, Salmonella, or E. coli vaccination&#xD;
&#xD;
          -  Tonsillectomy&#xD;
&#xD;
          -  Acute gastroenteritis in the past 2 months&#xD;
&#xD;
          -  Use of antibiotics in the past 2 months&#xD;
&#xD;
          -  Hypersensitivity to the vaccine, to formaldehyde or to any of the excipients (sodium&#xD;
             salts)&#xD;
&#xD;
          -  Pregnancy or lactating (pregnancy test will be performed on the vaccination days)&#xD;
&#xD;
          -  Not willing to drink raw milk&#xD;
&#xD;
          -  Allergic to milk or lactose-intolerant&#xD;
&#xD;
          -  Disease of GI tract, liver, gall bladder, kidneys, thyroid gland&#xD;
&#xD;
          -  Immune-compromised&#xD;
&#xD;
          -  Use of immunosuppressive drugs&#xD;
&#xD;
          -  Drug abuse, and not willing/able to stop this during the study&#xD;
&#xD;
          -  Excessive alcohol usage (men: &gt;4 consumptions/day or &gt;20 consumptions/week; women: &gt;3&#xD;
             consumptions/day or &gt;15 consumptions/week)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Els van Hoffen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NIZO Food Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>NIZO food research</name>
      <address>
        <city>Ede</city>
        <zip>6718 ZB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>March 28, 2017</last_update_submitted>
  <last_update_submitted_qc>March 28, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>immunity</keyword>
  <keyword>vaccination</keyword>
  <keyword>milk</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholera</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/NCT02238548
org study id: NL49042.081.14
nct id: NCT02238548
lead sponsor: 
collaborator: 
has dmc: No
Rationale: Infections are an important worldwide cause of death, both in elderly and young
      children. Therefore, support of immunity could help to reduce the incidence of infections. To
      screen the potential of specific foods or food ingredients to support immunity, oral
      vaccination can serve as a model. In this study, oral cholera vaccination will be applied in
      human adult volunteers, and used as a model to study the support of the immune response by
      raw milk.

      Objective: To investigate whether raw milk is able to enhance the immune response as induced
      by oral cholera vaccination.

      Study design: The study is designed as a single-blind randomized controlled trial of 4 weeks.

      Study population: Healthy subjects of 18-50 years of age.

      Intervention: Raw milk, obtained from farms that comply to the high quality requirements for
      production of raw milk, and that has been screened according to the safety criteria for raw
      milk.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Single (Investigator)
measure: Change in cholera toxin-specific IgA and IgG antibody level in nasal wash as a marker of the vaccination response
time frame: baseline and day 18
measure: Change in the cholera toxin-specific IgA and IgG antibody level in serum as a marker of the vaccination response
time frame: baseline and day 18
measure: Change in the cholera toxin-specific IgA antibody level in feces as a marker of the vaccination response
time frame: baseline and day 28
measure: Change in the cholera toxin-specific IgA and IgG antibody level in saliva as a marker of the vaccination response
time frame: baseline and day 18
measure: Change in the expression of tissue homing markers on IgA and IgG antibody-secreting B cells in peripheral blood as markers of the route of modulation of the vaccination response
time frame: baseline and day 18
measure: Cholera toxin-specific T cell proliferation as marker of modulation of the vaccination response
time frame: baseline and day 28
arm group label: Control group
arm group type: Placebo Comparator
description: Regular cholera vaccination
arm group label: Milk bolus
arm group type: Experimental
description: Cholera vaccination - raw milk - bolus
arm group label: Milk controlled
arm group type: Experimental
description: Cholera vaccination - raw milk - controlled intake
intervention type: Biological
intervention name: Cholera vaccination
description: Oral cholera vaccination on day 0 and day 14
arm group label: Control group
arm group label: Milk bolus
arm group label: Milk controlled
other name: Dukoral
intervention type: Other
intervention name: Raw milk
arm group label: Milk bolus
arm group label: Milk controlled
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Els van Hoffen, PhD
role: Principal Investigator
affiliation: NIZO Food Research
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Cholera