Trial of Thiamine Supplementation in Cambodia

NCT ID: NCT03616288

Last Updated: 2021-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 335 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-28
• Study Completion Date: 2021-01-28

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)

Conditions

Thiamine Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Negative Control

placebo; 0 mg thiamine

Group Type: PLACEBO_COMPARATOR

thiamine (as thiamine hydrochloride)

Intervention Type: 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).

EAR Group

1.2 mg thiamine as thiamine hydrochloride

Group Type: EXPERIMENTAL

thiamine (as thiamine hydrochloride)

Intervention Type: 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

2.4 mg thiamine as thiamine hydrochloride

Group Type: EXPERIMENTAL

thiamine (as thiamine hydrochloride)

Intervention Type: 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).

Positive Control

10 mg thiamine as thiamine hydrochloride

Group Type: EXPERIMENTAL

thiamine (as thiamine hydrochloride)

Intervention Type: 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).

Interventions

thiamine (as thiamine hydrochloride)

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).

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sackler Institute for Nutrition Science

OTHER

Sponsor Role: collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

Helen Keller International

OTHER

Sponsor Role: collaborator

NCHADS - Ministry of Health of Cambodia

OTHER

Sponsor Role: collaborator

Ministry of Planning, Cambodia

UNKNOWN

Sponsor Role: collaborator

South Australian Health and Medical Research Institute

OTHER

Sponsor Role: collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: collaborator

University of Oregon

OTHER

Sponsor Role: collaborator

Mount Saint Vincent University

OTHER

Sponsor Role: lead

Responsible Party

Kyly Whitfield

Assistant Professor, Department of Applied Human Nutrition

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kyly C Whitfield, PhD

Role: PRINCIPAL_INVESTIGATOR

Mount Saint Vincent University

Locations

Helen Keller International

Kampong Thom, Kapmong Thom Province, Cambodia

Countries

Cambodia

References

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.

Reference Type: DERIVED

PMID: 39699595 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33829271 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31292183 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

112NECHR

Identifier Type: OTHER

Identifier Source: secondary_id

MSVUREB2017-141

Identifier Type: -

Identifier Source: org_study_id