<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/NCT03258385</url>
  </required_header>
  <id_info>
    <org_study_id>PR-16003</org_study_id>
    <nct_id>NCT03258385</nct_id>
  </id_info>
  <brief_title>Vitamin B12 Supplementation to Improve B12 Status and Child Development</brief_title>
  <official_title>Effects of Vitamin B12 Fortified Milk Supplementation During Pregnancy and 6 Month Postpartum to Improve B12 Status and Child Development</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>International Centre for Diarrhoeal Disease Research, Bangladesh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nestlé Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>International Centre for Diarrhoeal Disease Research, Bangladesh</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>
      Impaired vitamin B12 (B12) status during pregnancy is associated with increased risk of birth&#xD;
      defects and common complications (e.g. intrauterine growth restriction, neural tube defects),&#xD;
      and possibly immune function impairment. The newborns and infants of B12-deficient mothers&#xD;
      have low B12 stores at birth, further exacerbated by a very low concentration of B12 in&#xD;
      breast milk that may hinder their growth and development. In regions such as Bangladesh, many&#xD;
      women of reproductive age have inadequate B12 status, probably due to low intake of animal&#xD;
      source food. Vitamin B12 intake and status in pregnancy and lactation is potentially&#xD;
      insufficient to prevent impaired child development and immune function related to inadequate&#xD;
      B12 status. The investigators hypothesize that prolonged vitamin B12 supplementation through&#xD;
      fortified milk starting from early pregnancy up to 6 mo-postpartum will improve: (1)&#xD;
      biomarkers of vitamin B12 status in mothers-infant pairs (2) vaccine specific adaptive&#xD;
      immunity in infants; (3) neurological and cognitive function in infants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators aim to conduct a double-blind, randomized trial, to investigate the effects&#xD;
      of B12-fortified milk on maternal and infant B12 status, immune function and child&#xD;
      development. Pregnant women (n=148) will be randomized to receive B12-fortified milk (100&#xD;
      μg/day) or milk without fortification. The daily supplementation beginning at the baseline&#xD;
      visit (GW 11-14) will continue until 6 mo-postpartum. Biomarkers of B12 status will be&#xD;
      measured in mothers (GW 11-14 and 6-mo postpartum) and infants (3 and 6-mo). Infant&#xD;
      development (6 and 12-mo) will be evaluated by Bayley Scales of Infant and Toddler&#xD;
      Development. Immune responses will be measured in infant at 3 and 6-mo. Data on socioeconomic&#xD;
      status, dietary diversity, and anthropometric indices will be recorded at baseline.&#xD;
      Additional tests in mothers include screening for H. pylori and plasma gastrin.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2017</start_date>
  <completion_date type="Actual">October 30, 2021</completion_date>
  <primary_completion_date type="Actual">October 30, 2021</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>Health Services Research</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in concentrations of biomarkers of vitamin B12 in mother-child pairs</measure>
    <time_frame>Baseline and 6 months postpartum</time_frame>
    <description>The investigators will determine the change in concentrations of biomarkers of B12 ( based on measurement of B12, MMA, tHcy, holoTC, cB12, folate in plasma; B12 in breast milk)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vaccine specific immunity in infants</measure>
    <time_frame>6 months</time_frame>
    <description>The investigators will determine the concentrations of vaccine specific IgA and IgG in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cognitive, Language and Motor Composite Score</measure>
    <time_frame>12 months</time_frame>
    <description>The outcomes are measured by Bayley-III test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nuroinflammatory cytokines</measure>
    <time_frame>12 months</time_frame>
    <description>The investigators will determine the change in concentrations of EGF and TNF-α in plasma</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">155</enrollment>
  <condition>Early Pregnancy</condition>
  <arm_group>
    <arm_group_label>Vitamin B12-fortified UHT milk</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Supplementation group (N=74) that will receive vitamin B12 fortified UHT milk daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Plain UHT milk</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo group (N=74) that will receive plain UHT milk daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin B12 fortified UHT milk</intervention_name>
    <description>Daily intake of 200 mL of UHT milk fortified with 100 µg vitamin B12</description>
    <arm_group_label>Vitamin B12-fortified UHT milk</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Plain UHT milk</intervention_name>
    <description>Daily intake of 200 mL of plain UHT milk</description>
    <arm_group_label>Plain UHT milk</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1. 18 - 35 y old 2. 11-14 wk pregnant (based on last menstrual period) 3. Willing to stay&#xD;
        in Dhaka during pregnancy and remain in the area for the 12 mo following recruitment 4.&#xD;
        Willing to be admitted in the clinic for delivery 5. Intends to exclusively or&#xD;
        predominantly breastfeed infant until 6 mo of age&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        1. Women with severe anemia; Hb concentration &lt;70 g/L 2. History or presence of systemic&#xD;
        disease such as Diabetes mellitus, Hypertension 3. History of previous complicated&#xD;
        pregnancies, pre-term delivery, or abortion 4. Current use of supplements containing&#xD;
        vitamin B12 5. Children with acute illness or features suggestive of any chronic disease&#xD;
        such as tuberculosis, any congenital anomalies such as cleft lip or palate.&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Towfida J Siddiqua, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>International Centre for Diarrhoeal Disease Research, Bangladesh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maternal and Child Health Training Institute</name>
      <address>
        <city>Dhaka</city>
        <zip>1205</zip>
        <country>Bangladesh</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bangladesh</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>August 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>January 15, 2023</last_update_submitted>
  <last_update_submitted_qc>January 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin B12, Fortified milk, Immunity, Child development</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin B 12</mesh_term>
    <mesh_term>Hydroxocobalamin</mesh_term>
  </intervention_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/NCT03258385
org study id: PR-16003
nct id: NCT03258385
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Impaired vitamin B12 (B12) status during pregnancy is associated with increased risk of birth
      defects and common complications (e.g. intrauterine growth restriction, neural tube defects),
      and possibly immune function impairment. The newborns and infants of B12-deficient mothers
      have low B12 stores at birth, further exacerbated by a very low concentration of B12 in
      breast milk that may hinder their growth and development. In regions such as Bangladesh, many
      women of reproductive age have inadequate B12 status, probably due to low intake of animal
      source food. Vitamin B12 intake and status in pregnancy and lactation is potentially
      insufficient to prevent impaired child development and immune function related to inadequate
      B12 status. The investigators hypothesize that prolonged vitamin B12 supplementation through
      fortified milk starting from early pregnancy up to 6 mo-postpartum will improve: (1)
      biomarkers of vitamin B12 status in mothers-infant pairs (2) vaccine specific adaptive
      immunity in infants; (3) neurological and cognitive function in infants.
The investigators aim to conduct a double-blind, randomized trial, to investigate the effects
      of B12-fortified milk on maternal and infant B12 status, immune function and child
      development. Pregnant women (n=148) will be randomized to receive B12-fortified milk (100
      μg/day) or milk without fortification. The daily supplementation beginning at the baseline
      visit (GW 11-14) will continue until 6 mo-postpartum. Biomarkers of B12 status will be
      measured in mothers (GW 11-14 and 6-mo postpartum) and infants (3 and 6-mo). Infant
      development (6 and 12-mo) will be evaluated by Bayley Scales of Infant and Toddler
      Development. Immune responses will be measured in infant at 3 and 6-mo. Data on socioeconomic
      status, dietary diversity, and anthropometric indices will be recorded at baseline.
      Additional tests in mothers include screening for H. pylori and plasma gastrin.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in concentrations of biomarkers of vitamin B12 in mother-child pairs
time frame: Baseline and 6 months postpartum
description: The investigators will determine the change in concentrations of biomarkers of B12 ( based on measurement of B12, MMA, tHcy, holoTC, cB12, folate in plasma; B12 in breast milk)
measure: Vaccine specific immunity in infants
time frame: 6 months
description: The investigators will determine the concentrations of vaccine specific IgA and IgG in plasma
measure: Cognitive, Language and Motor Composite Score
time frame: 12 months
description: The outcomes are measured by Bayley-III test
measure: Nuroinflammatory cytokines
time frame: 12 months
description: The investigators will determine the change in concentrations of EGF and TNF-α in plasma
arm group label: Vitamin B12-fortified UHT milk
arm group type: Active Comparator
description: Supplementation group (N=74) that will receive vitamin B12 fortified UHT milk daily
arm group label: Plain UHT milk
arm group type: Placebo Comparator
description: Placebo group (N=74) that will receive plain UHT milk daily
intervention type: Dietary Supplement
intervention name: Vitamin B12 fortified UHT milk
description: Daily intake of 200 mL of UHT milk fortified with 100 µg vitamin B12
arm group label: Vitamin B12-fortified UHT milk
intervention type: Dietary Supplement
intervention name: Plain UHT milk
description: Daily intake of 200 mL of plain UHT milk
arm group label: Plain UHT milk
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Towfida J Siddiqua, PhD
role: Principal Investigator
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
facility: 
country: Bangladesh
responsible party type: Sponsor
mesh term: Vitamin B 12
mesh term: Hydroxocobalamin