Clinical trial NCT03616288: Trial of Thiamine Supplementation in Cambodia
Official title: Improving Estimates of the Global Burden of Thiamine Deficiency Disorders and Approaches to Their Control: Trial of Thiamine Supplementation in Cambodia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thiamine Deficiency
Lead sponsor: Mount Saint Vincent University
Sponsor class: OTHER
Collaborators: name: Sackler Institute for Nutrition Science
name: Bill and Melinda Gates Foundation
name: Helen Keller International
name: NCHADS - Ministry of Health of Cambodia
name: Ministry of Planning, Cambodia
name: South Australian Health and Medical Research Institute
name: Institut de Recherche pour le Developpement
name: University of Oregon
First posted: 2018-08-06
Enrollment: 335
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo controlled, double-blinded, four-parallel arm, multicentre trial
Primary purpose: PREVENTION

Brief summary: Beriberi is a potentially fatal disease caused by vitamin B1 (thiamine) deficiency that still occurs in Southeast Asia despite near eradication elsewhere. Mothers with a diet low in thiamine produce thiamine-poor milk, putting their infants at a high risk of developing thiamine deficiency and beriberi. There is also a growing body of evidence suggesting thiamine deficiency not severe enough to cause clinical symptoms may negatively effect cognitive development and functioning of the infant. Since human milk should be the sole source of nutrition for babies during the first six months, maternal thiamine intake must be improved to combat this disease.

The investigators' recent study of thiamine-fortified fish sauce in Cambodia showed that fortification could increase maternal and infant thiamine status'. However, centrally produced fish sauce may not reach the poorest communities who make their own fish sauce, and fish sauce is not consumed in all regions where we find thiamine deficiency. Salt, by contrast, is a common condiment in most regions of the world and has proven to be a successful global fortification vehicle for iodine.

Suboptimal maternal thiamine intake puts exclusively breastfed infants at risk of low thiamine status, impaired cognitive development, and infantile beriberi, which can be fatal. Thiamine fortification of salt is a potentially low-cost and sustainable means of combating suboptimal thiamine status; however knowledge gaps must be filled before thiamine fortification can proceed. In this study, mothers will consume thiamine supplements in order to model the thiamine dose required to optimize human milk thiamine concentrations for the prevention of beriberi. Other thiamine biomarkers will be assessed, and usual salt intake will be measured. Finally, the investigators will assess the effects of early-life thiamine exposure on infant neuro-cognitive development.

Detailed description: (see full protocol)

Eligibility criteria: Inclusion Criteria:

Mothers of a newborn who:

* are aged 18 - 45 years
* had a recent normal pregnancy (i.e. no known chronic conditions, no preeclampsia, gestational diabetes etc), and the singleton infant was born without complications (e.g. low birth weight (\<2.5 kg), tongue tie, cleft palate)
* are intending to exclusively breastfeed for six months
* reside in Kampong Thom province, Cambodia, and are not planning to move in the next six months
* are willing to consume one capsule daily from 2 weeks through to 24 weeks postpartum
* are willing for her entire household consume only salt provided by the study team
* are willing for the following biological samples to be collected: a maternal venous blood sample and human milk sample at 2 weeks postpartum, a human milk sample at 4 and 12 weeks postpartum, and maternal and infant blood samples and a human milk sample at 24 weeks postpartum.

Exclusion Criteria:

Mothers of a newborn who:

* are currently taking or has taken thiamine-containing supplements over the past 4 months
* are currently participating in nutrition programs beyond normal care

Primary outcomes:
measure: Human milk total thiamine concentration
timeFrame: 24 weeks postpartum
Secondary outcomes:
Other outcomes:
measure: Infant thiamine diphosphate concentrations (ThDP)
timeFrame: 24 weeks postnatal
measure: Human milk total thiamine concentrations
timeFrame: 4 and 12 weeks postpartum
measure: Infant transketolase activity
timeFrame: 24 weeks postnatal
measure: Maternal ThDP (dose response)
timeFrame: 24 weeks postpartum
measure: Maternal transketolase activity (dose response)
timeFrame: 24 weeks postpartum
measure: Human milk total thiamine concentrations
timeFrame: 4, 12, and 24 weeks postpartum
measure: Maternal ThDP (by arm)
timeFrame: 24 weeks postpartum
measure: Maternal transketolase activity (by arm)
timeFrame: 24 weeks postpartum
measure: Household salt intake
timeFrame: within 2 and 24 weeks postpartum
measure: Salt intake of household members
timeFrame: within 2 and 24 weeks postpartum
measure: Sodium intake of women
timeFrame: within 2 and 24 weeks postpartum
measure: Mullen scores
timeFrame: 24 and 52 weeks postnatal
measure: Visual paired comparison
timeFrame: 24 and 52 weeks postnatal
measure: Language Preference Task
timeFrame: 24 weeks postnatal
measure: Oculomotor scores
timeFrame: 24 weeks postnatal
measure: Inflammation
timeFrame: 24 weeks postnatal
Locations:
city: Kampong Thom
country: Cambodia
facility: Helen Keller International
state: Kapmong Thom Province
Study officials:
affiliation: Mount Saint Vincent University
name: Kyly C Whitfield, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gallant J, Chan K, Green TJ, Wieringa FT, Leemaqz S, Ngik R, Measelle JR, Baldwin DA, Borath M, Sophonneary P, Yelland LN, Hampel D, Shahab-Ferdows S, Allen LH, Jones KS, Koulman A, Parkington DA, Meadows SR, Kroeun H, Whitfield KC. Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial. Am J Clin Nutr. 2021 Jul 1;114(1):90-100. doi: 10.1093/ajcn/nqab052.
citation: Whitfield KC, Kroeun H, Green T, Wieringa FT, Borath M, Sophonneary P, Measelle JR, Baldwin D, Yelland LN, Leemaqz S, Chan K, Gallant J. Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial. BMJ Open. 2019 Jul 9;9(7):e029255. doi: 10.1136/bmjopen-2019-029255.