Thiamin Fortified Fish Sauce as a Means of Combating Infantile Beriberi in Rural Cambodia
Condition: Thiamin Deficiency
MeSH terms: Thiamine Deficiency; Beriberi
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Thiamin fortified fish sauce (low concentration); Thiamin fortified fish sauce (higher concentration); Placebo fish sauce
Intervention type(s): Other; Other; Other
Intervention description(s): 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.; 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.; 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.
Intervention MeSH terms: Thiamine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: thiamin; thiamin diphosphate; beriberi; Cambodia; fish sauce; fortification; pregnancy; breastfeeding; childbearing age