xml: <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/NCT06027801</url>
    </required_header>
    <id_info>
      <org_study_id>VEST</org_study_id>
      <nct_id>NCT06027801</nct_id>
    </id_info>
    <brief_title>Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity</brief_title>
    <official_title>Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity: a Randomized Controlled Trial in Iron Deficient Thai Women</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Oxford</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Mahidol University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Ministry of Health, Thailand</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Oxford</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>
        Iron deficiency (ID) anaemia (IDA) is a global public health problem, with the highest&#xD;
        prevalence in Africa and in South-East Asia. While immunization programs have achieved high&#xD;
        global coverage, vaccines often underperform in low- and middle-income countries (LMIC). The&#xD;
        cause remains uncertain, but undernutrition, including ID, likely plays a role. Our recent in&#xD;
        vitro and in vivo studies have shown the importance of iron status in adaptive immunity and&#xD;
        vaccine response. Hypoferremia blunted T cell, B cell, and neutralizing antibody responses to&#xD;
        influenza virus infection in mice, allowing the virus to persist. Iron deficient anaemic&#xD;
        Kenyan women receiving intravenous iron at time of vaccination had a better immune response&#xD;
        to the first dose of the ChAdOx Coronavirus 19 (COVID-19) vaccine and yellow fever vaccine.&#xD;
        Japanese encephalitis and typhoid fever are endemic in Thailand. Vaccines are available but&#xD;
        show variable efficacy. Whether ID impairs adult vaccine response to the live attenuated&#xD;
        Japanese encephalitis (JE) and the Typhoid Vi polysaccharide (Vi-PS) vaccine and whether iron&#xD;
        repletion via iron fortification improves vaccine response is uncertain.&#xD;
  &#xD;
        The objective of this study is to assess whether IDA in Thai women impairs immune response to&#xD;
        the JE and the Typhoid Vi-PS vaccine and whether fortification iron improves their response.&#xD;
  &#xD;
        In this double-blind randomized controlled trial, IDA women will be assigned to two study&#xD;
        groups: group 1 (fortification group) will receive iron-fortified biscuits (15mg iron as&#xD;
        ferrous fumarate) for 56 days; group 2 (control group) will receive non-fortified biscuits&#xD;
        for 56 days. All women will receive live attenuated JE and Typhoid Vi-PS vaccine on study day&#xD;
        28. Vaccine response will be measured 28 days after vaccination (on day 56) in both groups.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</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>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Immunoglobulin G (IgG) concentrations against Salmonella Typhi</measure>
      <time_frame>day 28 (time of vaccination)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunoglobulin A (IgA) concentrations against Salmonella Typhi</measure>
      <time_frame>day 28 (time of vaccination)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunoglobulin G (IgG) concentrations against Salmonella Typhi</measure>
      <time_frame>day 56 (4 weeks after vaccination)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Immunoglobulin A (IgA) concentrations against Salmonella Typhi</measure>
      <time_frame>day 56 (4 weeks after vaccination)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Neutralizing antibodies against Japanese encephalitis</measure>
      <time_frame>day 28 (time of vaccination)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Neutralizing antibodies against Japanese encephalitis</measure>
      <time_frame>day 56 (4 weeks after vaccination)</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Hemoglobin concentration (g/dL)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemoglobin concentration (g/dL)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hemoglobin concentration (g/dL)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>serum iron (SFe) concentration (ng/µl)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>serum iron (SFe) concentration (ng/µl)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>serum iron (SFe) concentration (ng/µl)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>total iron binding capacity (µg/dL)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>total iron binding capacity (µg/dL)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>total iron binding capacity (µg/dL)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>transferrin saturation (TSAT) (%)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>transferrin saturation (TSAT) (%)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>transferrin saturation (TSAT) (%)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>plasma ferritin (PF) concentration (µg/L)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>plasma ferritin (PF) concentration (µg/L)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>plasma ferritin (PF) concentration (µg/L)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>soluble transferrin receptor (sTfR) concentration (mg/L)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>soluble transferrin receptor (sTfR) concentration (mg/L)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>soluble transferrin receptor (sTfR) concentration (mg/L)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-reactive protein (CRP) concentration (mg/L)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-reactive protein (CRP) concentration (mg/L)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>C-reactive protein (CRP) concentration (mg/L)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>alpha-glycoprotein (AGP) concentration (g/L)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>alpha-glycoprotein (AGP) concentration (g/L)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>alpha-glycoprotein (AGP) concentration (g/L)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>retinol-binding protein concentration (µmol/L)</measure>
      <time_frame>day 0</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>retinol-binding protein concentration (µmol/L)</measure>
      <time_frame>day 28</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>retinol-binding protein concentration (µmol/L)</measure>
      <time_frame>day 56</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">150</enrollment>
    <condition>Iron Deficiency Anemia</condition>
    <arm_group>
      <arm_group_label>Iron fortification group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants assigned to this group will receive iron-fortified cookies daily for the whole study duration</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants assigned to this group will receive the same cookies containing no iron daily for the whole study duration</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Iron-fortified cookies</intervention_name>
      <description>Study cookies fortified with ferrous fumarate, providing 15 mg of elemental iron in each portion.</description>
      <arm_group_label>Iron fortification group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Japanese encephalitis (JE) vaccine</intervention_name>
      <description>All participants will be administered the live attenuated JE vaccine</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Iron fortification group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Typhoid Vi polysaccharide (Vi-PS) vaccine</intervention_name>
      <description>All participants will be administered the typhoid Vi-PS vaccine</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Iron fortification group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>non-fortified cookies</intervention_name>
      <description>Study cookies containing no iron</description>
      <arm_group_label>Control group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Participant is willing and able to give informed consent for participation in the&#xD;
               trial.&#xD;
  &#xD;
            -  Female aged 18-49 years.&#xD;
  &#xD;
            -  Diagnosed with anaemia (i.e. hemoglobin (Hb) concentration &lt;12 g/dl), but no severe&#xD;
               anaemia (Hb &lt;8 g/dl), and iron deficiency (ZnPP &gt;40 µmol/mol)&#xD;
  &#xD;
            -  Anticipated residence in the area for the study duration&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant (confirmed by rapid test during screening and at time of vaccination),&#xD;
               lactating or planning pregnancy during the trial.&#xD;
  &#xD;
            -  Blood transfusion or intravenous iron treatment within 4 months of study start&#xD;
  &#xD;
            -  Major chronic infectious disease (e.g., tuberculosis, HIV+, hepatitis)&#xD;
  &#xD;
            -  Major chronic non-infectious disease (e.g., Type 1 or 2 diabetes, cancer)&#xD;
  &#xD;
            -  Treatment with supplemental iron two weeks prior to enrolment&#xD;
  &#xD;
            -  JE or typhoid vaccine within the past two years&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>49 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Nicole Stoffel, PhD</last_name>
      <phone>044 632 83 93</phone>
      <phone_ext>+41</phone_ext>
      <email>nicole.stoffel@rdm.ox.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Pattanee Winichagoon, Prof</last_name>
      <phone>66-2-800-2380</phone>
      <email>pattanee.win@mahidol.ac.th</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</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>Encephalitis, Japanese</mesh_term>
      <mesh_term>Typhoid Fever</mesh_term>
      <mesh_term>Encephalitis</mesh_term>
      <mesh_term>Anemia, Iron-Deficiency</mesh_term>
      <mesh_term>Iron Deficiencies</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Vaccines</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06027801
  org study id: VEST
  nct id: NCT06027801
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Iron deficiency (ID) anaemia (IDA) is a global public health problem, with the highest
        prevalence in Africa and in South-East Asia. While immunization programs have achieved high
        global coverage, vaccines often underperform in low- and middle-income countries (LMIC). The
        cause remains uncertain, but undernutrition, including ID, likely plays a role. Our recent in
        vitro and in vivo studies have shown the importance of iron status in adaptive immunity and
        vaccine response. Hypoferremia blunted T cell, B cell, and neutralizing antibody responses to
        influenza virus infection in mice, allowing the virus to persist. Iron deficient anaemic
        Kenyan women receiving intravenous iron at time of vaccination had a better immune response
        to the first dose of the ChAdOx Coronavirus 19 (COVID-19) vaccine and yellow fever vaccine.
        Japanese encephalitis and typhoid fever are endemic in Thailand. Vaccines are available but
        show variable efficacy. Whether ID impairs adult vaccine response to the live attenuated
        Japanese encephalitis (JE) and the Typhoid Vi polysaccharide (Vi-PS) vaccine and whether iron
        repletion via iron fortification improves vaccine response is uncertain.
  
        The objective of this study is to assess whether IDA in Thai women impairs immune response to
        the JE and the Typhoid Vi-PS vaccine and whether fortification iron improves their response.
  
        In this double-blind randomized controlled trial, IDA women will be assigned to two study
        groups: group 1 (fortification group) will receive iron-fortified biscuits (15mg iron as
        ferrous fumarate) for 56 days; group 2 (control group) will receive non-fortified biscuits
        for 56 days. All women will receive live attenuated JE and Typhoid Vi-PS vaccine on study day
        28. Vaccine response will be measured 28 days after vaccination (on day 56) in both groups.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Double (Participant, Investigator)
  measure: Immunoglobulin G (IgG) concentrations against Salmonella Typhi
  time frame: day 28 (time of vaccination)
  measure: Immunoglobulin A (IgA) concentrations against Salmonella Typhi
  time frame: day 28 (time of vaccination)
  measure: Immunoglobulin G (IgG) concentrations against Salmonella Typhi
  time frame: day 56 (4 weeks after vaccination)
  measure: Immunoglobulin A (IgA) concentrations against Salmonella Typhi
  time frame: day 56 (4 weeks after vaccination)
  measure: Neutralizing antibodies against Japanese encephalitis
  time frame: day 28 (time of vaccination)
  measure: Neutralizing antibodies against Japanese encephalitis
  time frame: day 56 (4 weeks after vaccination)
  measure: Hemoglobin concentration (g/dL)
  time frame: day 0
  measure: Hemoglobin concentration (g/dL)
  time frame: day 28
  measure: Hemoglobin concentration (g/dL)
  time frame: day 56
  measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
  time frame: day 0
  measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
  time frame: day 28
  measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
  time frame: day 56
  measure: serum iron (SFe) concentration (ng/µl)
  time frame: day 0
  measure: serum iron (SFe) concentration (ng/µl)
  time frame: day 28
  measure: serum iron (SFe) concentration (ng/µl)
  time frame: day 56
  measure: total iron binding capacity (µg/dL)
  time frame: day 0
  measure: total iron binding capacity (µg/dL)
  time frame: day 28
  measure: total iron binding capacity (µg/dL)
  time frame: day 56
  measure: transferrin saturation (TSAT) (%)
  time frame: day 0
  measure: transferrin saturation (TSAT) (%)
  time frame: day 28
  measure: transferrin saturation (TSAT) (%)
  time frame: day 56
  measure: plasma ferritin (PF) concentration (µg/L)
  time frame: day 0
  measure: plasma ferritin (PF) concentration (µg/L)
  time frame: day 28
  measure: plasma ferritin (PF) concentration (µg/L)
  time frame: day 56
  measure: soluble transferrin receptor (sTfR) concentration (mg/L)
  time frame: day 0
  measure: soluble transferrin receptor (sTfR) concentration (mg/L)
  time frame: day 28
  measure: soluble transferrin receptor (sTfR) concentration (mg/L)
  time frame: day 56
  measure: C-reactive protein (CRP) concentration (mg/L)
  time frame: day 0
  measure: C-reactive protein (CRP) concentration (mg/L)
  time frame: day 28
  measure: C-reactive protein (CRP) concentration (mg/L)
  time frame: day 56
  measure: alpha-glycoprotein (AGP) concentration (g/L)
  time frame: day 0
  measure: alpha-glycoprotein (AGP) concentration (g/L)
  time frame: day 28
  measure: alpha-glycoprotein (AGP) concentration (g/L)
  time frame: day 56
  measure: retinol-binding protein concentration (µmol/L)
  time frame: day 0
  measure: retinol-binding protein concentration (µmol/L)
  time frame: day 28
  measure: retinol-binding protein concentration (µmol/L)
  time frame: day 56
  arm group label: Iron fortification group
  arm group type: Experimental
  description: Participants assigned to this group will receive iron-fortified cookies daily for the whole study duration
  arm group label: Control group
  arm group type: Placebo Comparator
  description: Participants assigned to this group will receive the same cookies containing no iron daily for the whole study duration
  intervention type: Other
  intervention name: Iron-fortified cookies
  description: Study cookies fortified with ferrous fumarate, providing 15 mg of elemental iron in each portion.
  arm group label: Iron fortification group
  intervention type: Biological
  intervention name: Japanese encephalitis (JE) vaccine
  description: All participants will be administered the live attenuated JE vaccine
  arm group label: Control group
  arm group label: Iron fortification group
  intervention type: Biological
  intervention name: Typhoid Vi polysaccharide (Vi-PS) vaccine
  description: All participants will be administered the typhoid Vi-PS vaccine
  arm group label: Control group
  arm group label: Iron fortification group
  intervention type: Other
  intervention name: non-fortified cookies
  description: Study cookies containing no iron
  arm group label: Control group
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: 49 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Nicole Stoffel, PhD
  phone: 044 632 83 93
  phone ext: +41
  email: nicole.stoffel@rdm.ox.ac.uk
  last name: Pattanee Winichagoon, Prof
  phone: 66-2-800-2380
  email: pattanee.win@mahidol.ac.th
  responsible party type: Sponsor
  mesh term: Encephalitis, Japanese
  mesh term: Typhoid Fever
  mesh term: Encephalitis
  mesh term: Anemia, Iron-Deficiency
  mesh term: Iron Deficiencies
  mesh term: Vaccines
  sharing ipd: No