<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/NCT02221063</url>
  </required_header>
  <id_info>
    <org_study_id>H14-00103</org_study_id>
    <secondary_id>S6 0490-01-10</secondary_id>
    <nct_id>NCT02221063</nct_id>
  </id_info>
  <brief_title>Thiamin Fortified Fish Sauce as a Means of Combating Infantile Beriberi in Rural Cambodia</brief_title>
  <official_title>Thiamin Fortified Fish Sauce as a Means of Combating Infantile Beriberi in Rural Cambodia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Helen Keller International</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Grand Challenges Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>International Development Research Centre, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of British Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether consumption of thiamin fortified fish sauce&#xD;
      over 6 months increases the thiamin status of women to a level consistent with a low risk of&#xD;
      infantile beriberi. The investigators hypothesize that consumption of thiamin-fortified fish&#xD;
      sauce will increase red blood cell thiamin concentrations, an indicator of thiamin status, in&#xD;
      women consuming thiamin-fortified fish sauce, while concentrations will not change in women&#xD;
      consuming a placebo fish sauce that does not contain thiamin.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Purpose The purpose of this three-armed, double blind randomized control trial is to&#xD;
      determine whether thiamin-fortified fish sauce is an efficacious means of increasing dietary&#xD;
      thiamin intake in Cambodian women to a level that increases erythrocyte thiamin diphosphate&#xD;
      (TDP) concentrations to a level consistent with a low risk of infantile beriberi. Two groups&#xD;
      of women will participate in this study: women of childbearing age (18-45y; n=270), and&#xD;
      pregnant women (18-45y; ~26 weeks pregnant at baseline; n=90).&#xD;
&#xD;
      Hypothesis Intervention with thiamin-fortified fish sauce will increase women's TDP&#xD;
      concentrations to levels consistent with a low risk of infantile beriberi compared to those&#xD;
      receiving the control fish sauce.&#xD;
&#xD;
      Study Justification Beriberi is a micronutrient deficiency disease caused by a lack of&#xD;
      thiamin (vitamin B1) in the diet. Infantile beriberi is common in Southeast Asia.&#xD;
&#xD;
      Beriberi, a disease caused by severe thiamin deficiency, is rare in the west but is thought&#xD;
      to be more common in developing countries, particularly those in Southeast Asia. In infants,&#xD;
      beriberi presents with symptoms of heart failure and is fatal unless thiamin treatment is&#xD;
      initiated immediately. Beriberi typically presents in exclusively breastfed infants whose&#xD;
      mothers have suboptimal thiamin status and consequently have low breast milk thiamin&#xD;
      concentrations. Maternal thiamin deficiency in Cambodia is likely a result of multiple&#xD;
      factors: the high consumption of white, polished rice, which has been removed from its&#xD;
      B-vitamin-containing husk, a lack of parboiling rice, and low dietary diversity. Improving&#xD;
      the thiamin status of pregnant and lactating women is essential for combating infantile&#xD;
      beriberi. Fortification of a food staple has proven to be a successful strategy in increasing&#xD;
      population levels of thiamin because as a 'passive' intervention, it requires little to no&#xD;
      behavior change. Fish sauce is an ideal vehicle for thiamin fortification: it is consumed&#xD;
      daily in consistently high quantities, and is produced in centralized plants, and has been&#xD;
      successfully used in Cambodia and Vietnam as a vehicle for iron fortification.&#xD;
&#xD;
      Research Method All villages in Prey Veng province that are not already involved in an active&#xD;
      intervention (for example, homestead food production, micronutrient powder intervention etc)&#xD;
      will be randomized. A Khmer-speaking research assistant will contact the Village Chief and/or&#xD;
      Village Health Volunteer in the first village on the randomized list and determine the number&#xD;
      of eligible women of childbearing age and pregnant women (~26 weeks) in that village. The&#xD;
      research assistant will move down the randomized list of villages until 360 participants have&#xD;
      been enrolled. The investigators expect enrolment from approximately 10 villages.&#xD;
&#xD;
      A trained, Khmer-speaking enumerator will conduct an interview in the participants home. The&#xD;
      questionnaire will collect demographic data, as well as information on dietary intake&#xD;
      (including fish sauce), thoughts and perceptions of fortified products, and knowledge of&#xD;
      thiamin deficiency and beriberi. Once the questionnaire is complete the participant will walk&#xD;
      with the interviewer to a central meeting spot within the village (typically the Village&#xD;
      Chief's home) to complete anthropometric measurements (height and weight). The next morning&#xD;
      the participant will travel to the local health centre for a non-fasted blood draw.&#xD;
&#xD;
      Once the participant completes the baseline questionnaire, anthropometrics, and blood&#xD;
      collection she will be randomly assigned to one of the three treatment groups: low&#xD;
      concentration thiamin-iron-fortified fish sauce (2mg thiamin/mL fish sauce + iron), higher&#xD;
      concentration thiamin-fortified fish sauce (8mg thiamin/mL fish sauce + iron), or placebo:&#xD;
      iron-fortified fish sauce. The bottles and labels of the three fish sauces will be identical&#xD;
      in appearance, except for a code that differentiates the sauces.&#xD;
&#xD;
      All participants will be visited biweekly for monitoring and evaluation of fish sauce&#xD;
      consumption. Fish sauce will be distributed during these visits to ensure that there are no&#xD;
      'stock outs' of fish sauce during the study.&#xD;
&#xD;
      Within the first month of the study all participants will attend an educational workshop with&#xD;
      training regarding dietary thiamin intake, thiamin deficiency and beriberi, and infant and&#xD;
      young child feeding (IYCF) practices.&#xD;
&#xD;
      Anthropometric measurements (weight and length) will be taken within 72 hours of the birth of&#xD;
      the participant's infant (t~3 months).&#xD;
&#xD;
      At t~4 months, a subset of households (n=28) will participate in an Observed Weighed Fish&#xD;
      Sauce Record wherein a trained enumerator measure all fish sauce consumed by the participant&#xD;
      throughout one day. Two repeat observed weighed fish sauce records will be completed within a&#xD;
      2 week period.&#xD;
&#xD;
      At endline (t=6 months), the questionnaire, anthropometrics, and blood draw will be repeated&#xD;
      with all women. The investigators will also collect a venous blood sample (4mL) from the&#xD;
      infant, and a breast milk sample from mothers from the pregnant cohort. Investigators plan to&#xD;
      analyze all samples within two months of the endline sample collection, and will return to&#xD;
      the villages to share study findings with all participants at a community meeting (general&#xD;
      results shared), and then separately to share individual thiamin results one-on-one. All&#xD;
      participants will have already participated in an educational workshop highlighting the&#xD;
      importance of dietary thiamin intake, and the signs of thiamin deficiency and beriberi.&#xD;
      Individuals with suboptimal thiamin status will be encouraged to speak with their healthcare&#xD;
      provider, and will also be counselled using the materials that were previously used in the&#xD;
      educational workshop.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Erythrocyte thiamin diphosphate</measure>
    <time_frame>Baseline (t=0), Endline (t=6 months)</time_frame>
    <description>Measurement at baseline and endline for all women. Blood samples from infants of women recruited in the pregnancy cohort will be collected at endline only.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Breast milk thiamin concentration</measure>
    <time_frame>Endline (t=6 months)</time_frame>
    <description>Breast milk will collected only from those women recruited in the pregnancy cohort (n=90)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">366</enrollment>
  <condition>Thiamin Deficiency</condition>
  <arm_group>
    <arm_group_label>low [thiamin] fortified fish sauce</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fish sauce will contain 2 mg thiamin hydrochloride / mL fish sauce + iron (as NaFeEDTA)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>higher [thiamin] fortified fish sauce</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fish sauce will contain 8 mg thiamin hydrochloride / mL fish sauce + iron (as NaFeEDTA)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo fish sauce</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Fish sauce will contain only iron (as NaFeEDTA), no thiamin</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Thiamin fortified fish sauce (low concentration)</intervention_name>
    <description>Low concentration thiamin fortified fish sauce will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.</description>
    <arm_group_label>low [thiamin] fortified fish sauce</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Thiamin fortified fish sauce (higher concentration)</intervention_name>
    <description>Higher concentration thiamin fortified fish sauce will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.</description>
    <arm_group_label>higher [thiamin] fortified fish sauce</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo fish sauce</intervention_name>
    <description>Fish sauce fortified only with iron, not thiamin, will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.</description>
    <arm_group_label>Placebo fish sauce</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Women of Childbearing Age Cohort:&#xD;
&#xD;
          -  be the female head of their household,&#xD;
&#xD;
          -  have at least one child between 12 - 59 months of age at baseline,&#xD;
&#xD;
          -  be living in Prey Veng province, Cambodia, and not planning to move in the next six&#xD;
             months,&#xD;
&#xD;
          -  agree to exclusively feed her entire household the study fish sauce for six months,&#xD;
             and&#xD;
&#xD;
          -  be willing to provide venous blood samples at baseline and endline.&#xD;
&#xD;
        Pregnant Women Cohort:&#xD;
&#xD;
          -  be the female head of their household,&#xD;
&#xD;
          -  be ~3-8 mo pregnant with a singleton fetus at baseline,&#xD;
&#xD;
          -  have no prior history of preeclampsia, pre-term delivery, or birth defects,&#xD;
&#xD;
          -  know her approximate due date,&#xD;
&#xD;
          -  be living in Prey Veng province, Cambodia, and not planning to move in the next six&#xD;
             months,&#xD;
&#xD;
          -  agree to exclusively feed her entire household the study fish sauce for six months,&#xD;
             and&#xD;
&#xD;
          -  be willing to provide venous blood samples at baseline and endline, a breast milk&#xD;
             sample at endline, and to allow for a blood sample to be taken from her infant (aged&#xD;
             ~3 months) at endline.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Women of Childbearing Age Cohort:&#xD;
&#xD;
          -  not be receiving any other intervention (for example, homestead food production),&#xD;
&#xD;
          -  not be pregnant or hoping to become pregnant within the next 6 months, and&#xD;
&#xD;
          -  not be taking any supplement that contains thiamin.&#xD;
&#xD;
        Pregnant Women Cohort:&#xD;
&#xD;
          -  not be receiving any other intervention (for example, homestead food production), and&#xD;
&#xD;
          -  not be taking any supplement that contains thiamin.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tim J Green, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kyly C Whitfield, MSc</last_name>
    <role>Study Director</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Judy McLean, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of British Columbia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Zaman Talukder, MPH</last_name>
    <role>Study Chair</role>
    <affiliation>Helen Keller International</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>(Various Villages)</city>
        <state>Prey Veng</state>
        <country>Cambodia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Cambodia</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>May 24, 2016</last_update_submitted>
  <last_update_submitted_qc>May 24, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 25, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>thiamin</keyword>
  <keyword>thiamin diphosphate</keyword>
  <keyword>beriberi</keyword>
  <keyword>Cambodia</keyword>
  <keyword>fish sauce</keyword>
  <keyword>fortification</keyword>
  <keyword>pregnancy</keyword>
  <keyword>breastfeeding</keyword>
  <keyword>childbearing age</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thiamine Deficiency</mesh_term>
    <mesh_term>Beriberi</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thiamine</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/NCT02221063
org study id: H14-00103
secondary id: S6 0490-01-10
nct id: NCT02221063
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether consumption of thiamin fortified fish sauce
      over 6 months increases the thiamin status of women to a level consistent with a low risk of
      infantile beriberi. The investigators hypothesize that consumption of thiamin-fortified fish
      sauce will increase red blood cell thiamin concentrations, an indicator of thiamin status, in
      women consuming thiamin-fortified fish sauce, while concentrations will not change in women
      consuming a placebo fish sauce that does not contain thiamin.
Purpose The purpose of this three-armed, double blind randomized control trial is to
      determine whether thiamin-fortified fish sauce is an efficacious means of increasing dietary
      thiamin intake in Cambodian women to a level that increases erythrocyte thiamin diphosphate
      (TDP) concentrations to a level consistent with a low risk of infantile beriberi. Two groups
      of women will participate in this study: women of childbearing age (18-45y; n=270), and
      pregnant women (18-45y; ~26 weeks pregnant at baseline; n=90).

      Hypothesis Intervention with thiamin-fortified fish sauce will increase women's TDP
      concentrations to levels consistent with a low risk of infantile beriberi compared to those
      receiving the control fish sauce.

      Study Justification Beriberi is a micronutrient deficiency disease caused by a lack of
      thiamin (vitamin B1) in the diet. Infantile beriberi is common in Southeast Asia.

      Beriberi, a disease caused by severe thiamin deficiency, is rare in the west but is thought
      to be more common in developing countries, particularly those in Southeast Asia. In infants,
      beriberi presents with symptoms of heart failure and is fatal unless thiamin treatment is
      initiated immediately. Beriberi typically presents in exclusively breastfed infants whose
      mothers have suboptimal thiamin status and consequently have low breast milk thiamin
      concentrations. Maternal thiamin deficiency in Cambodia is likely a result of multiple
      factors: the high consumption of white, polished rice, which has been removed from its
      B-vitamin-containing husk, a lack of parboiling rice, and low dietary diversity. Improving
      the thiamin status of pregnant and lactating women is essential for combating infantile
      beriberi. Fortification of a food staple has proven to be a successful strategy in increasing
      population levels of thiamin because as a 'passive' intervention, it requires little to no
      behavior change. Fish sauce is an ideal vehicle for thiamin fortification: it is consumed
      daily in consistently high quantities, and is produced in centralized plants, and has been
      successfully used in Cambodia and Vietnam as a vehicle for iron fortification.

      Research Method All villages in Prey Veng province that are not already involved in an active
      intervention (for example, homestead food production, micronutrient powder intervention etc)
      will be randomized. A Khmer-speaking research assistant will contact the Village Chief and/or
      Village Health Volunteer in the first village on the randomized list and determine the number
      of eligible women of childbearing age and pregnant women (~26 weeks) in that village. The
      research assistant will move down the randomized list of villages until 360 participants have
      been enrolled. The investigators expect enrolment from approximately 10 villages.

      A trained, Khmer-speaking enumerator will conduct an interview in the participants home. The
      questionnaire will collect demographic data, as well as information on dietary intake
      (including fish sauce), thoughts and perceptions of fortified products, and knowledge of
      thiamin deficiency and beriberi. Once the questionnaire is complete the participant will walk
      with the interviewer to a central meeting spot within the village (typically the Village
      Chief's home) to complete anthropometric measurements (height and weight). The next morning
      the participant will travel to the local health centre for a non-fasted blood draw.

      Once the participant completes the baseline questionnaire, anthropometrics, and blood
      collection she will be randomly assigned to one of the three treatment groups: low
      concentration thiamin-iron-fortified fish sauce (2mg thiamin/mL fish sauce + iron), higher
      concentration thiamin-fortified fish sauce (8mg thiamin/mL fish sauce + iron), or placebo:
      iron-fortified fish sauce. The bottles and labels of the three fish sauces will be identical
      in appearance, except for a code that differentiates the sauces.

      All participants will be visited biweekly for monitoring and evaluation of fish sauce
      consumption. Fish sauce will be distributed during these visits to ensure that there are no
      'stock outs' of fish sauce during the study.

      Within the first month of the study all participants will attend an educational workshop with
      training regarding dietary thiamin intake, thiamin deficiency and beriberi, and infant and
      young child feeding (IYCF) practices.

      Anthropometric measurements (weight and length) will be taken within 72 hours of the birth of
      the participant's infant (t~3 months).

      At t~4 months, a subset of households (n=28) will participate in an Observed Weighed Fish
      Sauce Record wherein a trained enumerator measure all fish sauce consumed by the participant
      throughout one day. Two repeat observed weighed fish sauce records will be completed within a
      2 week period.

      At endline (t=6 months), the questionnaire, anthropometrics, and blood draw will be repeated
      with all women. The investigators will also collect a venous blood sample (4mL) from the
      infant, and a breast milk sample from mothers from the pregnant cohort. Investigators plan to
      analyze all samples within two months of the endline sample collection, and will return to
      the villages to share study findings with all participants at a community meeting (general
      results shared), and then separately to share individual thiamin results one-on-one. All
      participants will have already participated in an educational workshop highlighting the
      importance of dietary thiamin intake, and the signs of thiamin deficiency and beriberi.
      Individuals with suboptimal thiamin status will be encouraged to speak with their healthcare
      provider, and will also be counselled using the materials that were previously used in the
      educational workshop.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Erythrocyte thiamin diphosphate
time frame: Baseline (t=0), Endline (t=6 months)
description: Measurement at baseline and endline for all women. Blood samples from infants of women recruited in the pregnancy cohort will be collected at endline only.
measure: Breast milk thiamin concentration
time frame: Endline (t=6 months)
description: Breast milk will collected only from those women recruited in the pregnancy cohort (n=90)
arm group label: low [thiamin] fortified fish sauce
arm group type: Active Comparator
description: Fish sauce will contain 2 mg thiamin hydrochloride / mL fish sauce + iron (as NaFeEDTA)
arm group label: higher [thiamin] fortified fish sauce
arm group type: Active Comparator
description: Fish sauce will contain 8 mg thiamin hydrochloride / mL fish sauce + iron (as NaFeEDTA)
arm group label: Placebo fish sauce
arm group type: Placebo Comparator
description: Fish sauce will contain only iron (as NaFeEDTA), no thiamin
intervention type: Other
intervention name: Thiamin fortified fish sauce (low concentration)
description: Low concentration thiamin fortified fish sauce will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.
arm group label: low [thiamin] fortified fish sauce
intervention type: Other
intervention name: Thiamin fortified fish sauce (higher concentration)
description: Higher concentration thiamin fortified fish sauce will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.
arm group label: higher [thiamin] fortified fish sauce
intervention type: Other
intervention name: Placebo fish sauce
description: Fish sauce fortified only with iron, not thiamin, will be consumed ad libitum for 6 months, with biweekly monitoring and evaluation to assess fish sauce usage by household and to re-stock fish sauce within the home.
arm group label: Placebo fish sauce
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Tim J Green, PhD
role: Principal Investigator
affiliation: University of British Columbia
last name: Kyly C Whitfield, MSc
role: Study Director
affiliation: University of British Columbia
last name: Judy McLean, PhD
role: Study Chair
affiliation: University of British Columbia
last name: Zaman Talukder, MPH
role: Study Chair
affiliation: Helen Keller International
facility: 
country: Cambodia
responsible party type: Sponsor
mesh term: Thiamine Deficiency
mesh term: Beriberi
mesh term: Thiamine