<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/NCT03251495</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00097012</org_study_id>
    <secondary_id>R01AI137127</secondary_id>
    <nct_id>NCT03251495</nct_id>
  </id_info>
  <brief_title>Immunologic Responses to a Live Attenuated Oral Cholera Vaccine</brief_title>
  <official_title>Immunologic Responses to a Live Attenuated Oral Cholera Vaccine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the antibody response to the cholera&#xD;
      vaccine, Vaxchora®, in healthy subjects.&#xD;
&#xD;
      Investigators also seek to evaluate additional markers of the adaptive immune response&#xD;
      including plasmablasts, activated B cells, memory B cells, and T cell responses in healthy&#xD;
      subjects receiving cholera vaccine, produce monoclonal antibodies against cholera, and&#xD;
      evaluate the safety and reactogenicity in healthy subjects receiving cholera vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cholera is a life-threatening illness that causes diarrhea. Cholera is caused by eating or&#xD;
      drinking the Vibrio cholera bacteria. Each year, there are about 1.3 to 4.0 million cases of&#xD;
      cholera worldwide, resulting in 21,000 to 143,000 deaths. The bacteria is spread through&#xD;
      water or food that has stool in it. Up to 50 countries with limited access to clean water are&#xD;
      more likely to have outbreaks. In the United States most cases are linked to travel to these&#xD;
      countries; however, there are 10-15 cases acquired in the United States each year because of&#xD;
      undercooked seafood. Cholera spreads very easily. Illness from Cholera can vary from no&#xD;
      symptoms to severe watery diarrhea that can cause death by dehydration in a healthy person&#xD;
      within hours.&#xD;
&#xD;
      Vaxchora is a live attenuated cholera vaccine that protects against some cholera strains. It&#xD;
      has been approved by the FDA since June 2016. Since October, 2016, this vaccine has been&#xD;
      recommended for certain travelers 18 through 64 years of age going to cholera-affected areas.&#xD;
      The purpose of this study is to look at the immune responses to the FDA approved cholera&#xD;
      vaccine (Vaxchora®).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 29, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Positive Responders</measure>
    <time_frame>Day 29</time_frame>
    <description>Antibody titers will be collected to assess the level of immune response to vaccination. A positive responder is defined as a participant with a titer above 40 at day 29, or that shows a four-fold increase over baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasmablast Levels</measure>
    <time_frame>Day 29</time_frame>
    <description>Plasmablasts will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activated B Cell Levels</measure>
    <time_frame>Day 29</time_frame>
    <description>Activated B cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Memory B-Cell Levels</measure>
    <time_frame>Day 29</time_frame>
    <description>Memory B-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Memory T-Cell Levels</measure>
    <time_frame>Day 29</time_frame>
    <description>T-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Samples from which Monoclonal Antibodies Produced</measure>
    <time_frame>Day 29</time_frame>
    <description>The ability to isolate monoclonal antibodies will be assessed by study lab personnel.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Adverse Events</measure>
    <time_frame>Duration of Study (Up to 29 Days)</time_frame>
    <description>The number of solicited and unsolicited adverse events will be collected.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Serious Adverse Events</measure>
    <time_frame>Duration of Study (Up to 29 Days), Day 365</time_frame>
    <description>The number of serious adverse events will be collected.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Cholera</condition>
  <arm_group>
    <arm_group_label>Vaxchora Vaccination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy subjects will receive a single dose of oral live cholera vaccine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaxchora</intervention_name>
    <description>Vaxchora is a live attenuated cholera vaccine that provides immunity against V. cholerae serogroup O1. Participants will receive one single oral dose of 100 mL.</description>
    <arm_group_label>Vaxchora Vaccination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capable of informed consent and provision of written informed consent before any study&#xD;
             procedures&#xD;
&#xD;
          -  Capable of attending all study visits according to the study schedule&#xD;
&#xD;
          -  Are in good health, as determined by medical history and targeted physical exam&#xD;
             related to this history&#xD;
&#xD;
          -  Female subjects of childbearing age must have a negative urine pregnancy test before&#xD;
             study vaccination, and must use two forms of contraception to avoid pregnancy within&#xD;
             one month of Vaxchora administration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have an acute illness within 72 hours before vaccination&#xD;
&#xD;
          -  Have any acute or chronic medical condition that, in the opinion of the principal&#xD;
             investigator, would make vaccination unsafe or interfere with the evaluation of immune&#xD;
             response to study vaccination&#xD;
&#xD;
          -  Have a suppressed immune system as a result of illness, immunosuppressive medication,&#xD;
             chemotherapy, or radiation therapy within 3 years prior to study vaccination&#xD;
&#xD;
          -  Have taken oral or parenteral corticosteroids of any dose within 30 days before study&#xD;
             vaccination&#xD;
&#xD;
          -  Reside with individuals under the age of 2 or with an immunocompromised individuals&#xD;
&#xD;
          -  Have a known history of autoimmune disease&#xD;
&#xD;
          -  Have a history of Guillain-Barre Syndrome&#xD;
&#xD;
          -  Have plans to receive any vaccine from 28 days prior to study vaccination until Day 29&#xD;
&#xD;
          -  Has previously received a cholera vaccine or have a known history of V. Cholerae.&#xD;
&#xD;
          -  Have donated blood or blood products within 56 days before study vaccination, plan to&#xD;
             donate blood at any time during the 56-day duration of subject study participation, or&#xD;
             plan to donate blood within 56 days after the last blood draw&#xD;
&#xD;
          -  Have known hypersensitivity or allergy to any component of the vaccine or history of&#xD;
             anaphylaxis with a vaccine or vaccine component&#xD;
&#xD;
          -  Have allergy to tetracycline and/or ciprofloxacin&#xD;
&#xD;
          -  Are pregnant or breastfeeding or plan to within one month of vaccination&#xD;
&#xD;
          -  Traveled to a cholera endemic area and had traveler's diarrhea in the previous 5 years&#xD;
&#xD;
          -  Have abnormal stool pattern (fewer than 3 stools/ week or greater than 2 stools/ day)&#xD;
             or regular use of laxatives in the last 6 months&#xD;
&#xD;
          -  Have current or recent antibiotic use in the past 14 days&#xD;
&#xD;
          -  Are healthcare workers who have direct contact with patients who are&#xD;
             immunocompromised, have unstable medical conditions, or are under the age of 2&#xD;
&#xD;
          -  Are childcare caregivers who have direct contact with children who are 2 years or&#xD;
             younger.&#xD;
&#xD;
          -  Are employed in the food industry&#xD;
&#xD;
          -  Have received any vaccine within the previous 21 days&#xD;
&#xD;
          -  History of bleeding disorders or current use of warfarin, aspirin, heparin,&#xD;
             nonsteroidal anti-inflammatory drugs (NSAIDs) or other blood thinner/ anticoagulant&#xD;
             medications in the past week for subjects undergoing intestinal biopsies.&#xD;
&#xD;
          -  Use of benzodiazepines or narcotics for subjects undergoing intestinal biopsies 4&#xD;
             weeks prior to the procedure&#xD;
&#xD;
          -  Any contraindications to endoscopy/concerns of the anesthesiologist for subjects who&#xD;
             agree for esophagogastroduodenoscopy (EGD)/biopsies.&#xD;
&#xD;
          -  BMI &gt; 35 kg/m2&#xD;
&#xD;
          -  Have a diagnosis of any small bowel disease. This includes but is not limited to&#xD;
             inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, indeterminate&#xD;
             colitis, or microscopic colitis), small bowel obstruction, celiac disease, h/o small&#xD;
             bowel resection, small bowel lymphoma, Whipple's disease, primary Intestinal&#xD;
             lymphangiectasis, abdominal radiation.&#xD;
&#xD;
          -  Current medications for the treatment of Gastroesophageal reflux disease (GERD) or&#xD;
             dyspepsia&#xD;
&#xD;
          -  History of Helicobacter pylori (H. pylori) infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nadine Rouphael, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nadine Rouphael, MD</last_name>
    <phone>404-712-1370</phone>
    <email>nroupha@emory.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Hope Clinic of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadine Rouphael, MD</last_name>
      <phone>404-712-1370</phone>
      <email>nroupha@emory.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Nadine Rouphael</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Vaccination</keyword>
  <keyword>Contagious Diseases</keyword>
  <keyword>Tropical Medicine</keyword>
  <keyword>Infectious Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholera</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 13, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT03251495/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03251495
org study id: IRB00097012
secondary id: R01AI137127
nct id: NCT03251495
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary objective of this study is to evaluate the antibody response to the cholera
      vaccine, Vaxchora®, in healthy subjects.

      Investigators also seek to evaluate additional markers of the adaptive immune response
      including plasmablasts, activated B cells, memory B cells, and T cell responses in healthy
      subjects receiving cholera vaccine, produce monoclonal antibodies against cholera, and
      evaluate the safety and reactogenicity in healthy subjects receiving cholera vaccine.
Cholera is a life-threatening illness that causes diarrhea. Cholera is caused by eating or
      drinking the Vibrio cholera bacteria. Each year, there are about 1.3 to 4.0 million cases of
      cholera worldwide, resulting in 21,000 to 143,000 deaths. The bacteria is spread through
      water or food that has stool in it. Up to 50 countries with limited access to clean water are
      more likely to have outbreaks. In the United States most cases are linked to travel to these
      countries; however, there are 10-15 cases acquired in the United States each year because of
      undercooked seafood. Cholera spreads very easily. Illness from Cholera can vary from no
      symptoms to severe watery diarrhea that can cause death by dehydration in a healthy person
      within hours.

      Vaxchora is a live attenuated cholera vaccine that protects against some cholera strains. It
      has been approved by the FDA since June 2016. Since October, 2016, this vaccine has been
      recommended for certain travelers 18 through 64 years of age going to cholera-affected areas.
      The purpose of this study is to look at the immune responses to the FDA approved cholera
      vaccine (Vaxchora®).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Percentage of Positive Responders
time frame: Day 29
description: Antibody titers will be collected to assess the level of immune response to vaccination. A positive responder is defined as a participant with a titer above 40 at day 29, or that shows a four-fold increase over baseline.
measure: Plasmablast Levels
time frame: Day 29
description: Plasmablasts will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.
measure: Activated B Cell Levels
time frame: Day 29
description: Activated B cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.
measure: Memory B-Cell Levels
time frame: Day 29
description: Memory B-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.
measure: Memory T-Cell Levels
time frame: Day 29
description: T-cells will be collected via blood draw and isolated and assessed for counts by the study team. A positive response is defined as a four-fold increase over the baseline measure.
measure: Number of Samples from which Monoclonal Antibodies Produced
time frame: Day 29
description: The ability to isolate monoclonal antibodies will be assessed by study lab personnel.
measure: Number of Adverse Events
time frame: Duration of Study (Up to 29 Days)
description: The number of solicited and unsolicited adverse events will be collected.
measure: Number of Serious Adverse Events
time frame: Duration of Study (Up to 29 Days), Day 365
description: The number of serious adverse events will be collected.
arm group label: Vaxchora Vaccination
arm group type: Experimental
description: Healthy subjects will receive a single dose of oral live cholera vaccine.
intervention type: Drug
intervention name: Vaxchora
description: Vaxchora is a live attenuated cholera vaccine that provides immunity against V. cholerae serogroup O1. Participants will receive one single oral dose of 100 mL.
arm group label: Vaxchora Vaccination
criteria: 
gender: All
minimum age: 18 Years
maximum age: 49 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Nadine Rouphael, MD
role: Principal Investigator
affiliation: Emory University
last name: Nadine Rouphael, MD
phone: 404-712-1370
email: nroupha@emory.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Nadine Rouphael
investigator title: Professor
mesh term: Cholera
sharing ipd: No
provided document: 