Trial of Thiamine Supplementation in Cambodia

NCT03616288 | Completed

• 2 other identifiers: MSVUREB2017-141112NECHR
• Study Type: interventional
• Target: 335
• Locations: 1 country
• Sites: 1

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.

Conditions

Thiamine Deficiency

Outcome Measures

Primary Outcomes (1)

• Human milk total thiamine concentration

  To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases human milk total thiamine concentration at 24 weeks postpartum.

  24 weeks postpartum

Other Outcomes (16)

• Infant thiamine diphosphate concentrations (ThDP)

  24 weeks postnatal

• Human milk total thiamine concentrations

  4 and 12 weeks postpartum

• Infant transketolase activity

  24 weeks postnatal

Study Arms (4)

Negative Control

PLACEBO COMPARATOR

placebo; 0 mg thiamine

Dietary Supplement: thiamine (as thiamine hydrochloride)

EAR Group

EXPERIMENTAL

1.2 mg thiamine as thiamine hydrochloride

Dietary Supplement: thiamine (as thiamine hydrochloride)

Double EAR Group

EXPERIMENTAL

2.4 mg thiamine as thiamine hydrochloride

Dietary Supplement: thiamine (as thiamine hydrochloride)

Positive Control

EXPERIMENTAL

10 mg thiamine as thiamine hydrochloride

Dietary Supplement: thiamine (as thiamine hydrochloride)

Interventions

thiamine (as thiamine hydrochloride) DIETARY_SUPPLEMENT

Opaque capsules containing varying amounts of thiamine hydrochloride and cellulose filler. All thiamine is delivered as thiamine hydrochloride, calculated using a 1.271 correction factor (ratio of molecular weights of thiamine hydrochloride and thiamine).

Double EAR Group; EAR Group; Negative Control; Positive Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Saint Vincent University: lead
• Sackler Institute for Nutrition Science: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Helen Keller International: collaborator
• NCHADS - Ministry of Health of Cambodia: collaborator
• Ministry of Planning, Cambodia: collaborator
• South Australian Health and Medical Research Institute: collaborator
• Institut de Recherche pour le Developpement: collaborator
• University of Oregon: collaborator

Study Sites (1)

Helen Keller International

Kampong Thom, Kapmong Thom Province, Cambodia

Location

Related Publications (3)

• Baldwin DA, Measelle J, Gallivan L, Sanchirico A, Weinstein N, Bala A, Chan K, Gallant J, Borath M, Kroeun H, Wieringa FT, Green TJ, Whitfield KC. Language processing in breastfed infants at risk of thiamine deficiency benefits from maternal thiamine supplementation. Dev Psychol. 2025 Aug;61(8):1427-1440. doi: 10.1037/dev0001829. Epub 2024 Dec 19.

  PMID: 39699595 DERIVED

• 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.

  PMID: 33829271 DERIVED

• 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.

  PMID: 31292183 DERIVED

MeSH Terms

Conditions

Thiamine Deficiency

Interventions

Thiamine

Condition Hierarchy (Ancestors)

Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Kyly C Whitfield, PhD

  Mount Saint Vincent University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Applied Human Nutrition

Model Details: Randomized placebo controlled, double-blinded, four-parallel arm, multicentre trial

Study Record Dates

• First Submitted: July 31, 2018
• First Posted: August 6, 2018
• Study Start: August 28, 2018
• Primary Completion: May 5, 2020
• Study Completion: January 28, 2021
• Last Updated: February 24, 2021

Record last verified: 2021-02

Locations

CA (1)