Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR

NCT03626337 | Completed DMC

• 1 other identifier: 1329444
• Study Type: observational
• Target: 1,394
• Locations: 1 country
• Sites: 1

Brief Summary

A hospital- and community-based study in Luang Prabang, Lao PDR, which will include a group of hospitalized children 21 days to \<18 months of age who are diagnosed with symptoms compatible with thiamine deficiency disorder (TDD). Based on the infants' response to thiamine administration, children will be defined as either thiamine responsive disorder (TRD) cases or non-responders. A community-based comparison group of infants in the same age range will be included in the study to serve as a control group for identification of potential risk factors.

Conditions

Thiamine Deficiency

Outcome Measures

Primary Outcomes (1)

• Thiamine Responsive Disorder (TRD)

  Diagnosis of TRD will be determined based on improvements of initially abnormal physical findings such as hepatomegaly, heart rate, and respiratory rate, and resolution of echocardiographic findings of enlarged and poorly functioning ventricles

  48-72 hours

Secondary Outcomes (2)

• Biomarkers of whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac)

  Baseline

• Hemoglobin and biomarkers of other micronutrients (ferritin, transferrin receptor, retinol binding protein, erythrocyte glutathione reductase activation coefficient (EGRAC)), and inflammation (CRP, AGP)

  Baseline

Study Arms (2)

Hospital-based cohort

100 mg thiamine provided via intramuscular and/or intravenous injection (Thiamine 100 MG/ML) daily for 3 days

Drug: Thiamine 100 MG/ML

Community-based cohort

Sex-, age- and regionally matched comparison group

Interventions

Thiamine 100 MG/ML DRUG

100 mg thiamine provided as intramuscular injection

Also known as: Standard of care

Hospital-based cohort

Eligibility Criteria

• Age: 21 Days - 17 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Hospitalized children: Infants and children in the target age range (21 days to \<18 months), who are admitted to the participating hospitals, will be screened by hospital staff to determine the presence of at least one of the inclusion criteria Community-based cohort: A sex-, age- and regionally-similar comparison group will be enrolled based on the characteristics of the hospitalized group. Mothers of all participating infants will be invited to the study.

You may qualify if:

• Liver enlargement (\>2 cm below right costal margin on calm, supine exam)
• Edema
• Tachypnea (\> 60/min for 3-8 wks; \>50/min for 2-11 mo; \>40/min for 12 - 18 mo)
• Tachycardia (heart rate \>160/min for \<12 mo; \>120/min for 12 mo - 18 mo)
• Oxygen saturation (\<92%)
• Difficulty breathing (i.e. chest in-drawing, nasal flaring)
• Refusal to breastfeed or refusal of infant formula or food for greater than 24 hours
• Repetitive or recurring vomiting with no obvious other cause(i.e. vomiting \>3 times in past 24 hours)
• Persistent crying not relieved by soothing and feeding with no obvious other cause
• Hoarse voice/cry or loss of voice
• Nystagmus or other unusual eye movement
• Muscle twitching
• Loss of consciousness
• Convulsion
• Opisthotonus / abnormal posturing

You may not qualify if:

• \- None
• Children aged 21 days to \<18 months
• Residing in selected communities
• \- Severe acute illness warranting immediate hospital referral
• \- Mother of hospital-based study participant or community-based study participant
• Severe acute illness warranting immediate hospital referral
• Unable to provide informed consent due to reduced decision making ability

Sponsors & Collaborators

• University of California, Davis: lead
• Lao Tropical and Public Health Institute: collaborator

Study Sites (1)

Lao Friends Hospital for Children

Luang Prabang, Laos

Location

Related Publications (5)

• Hess SY, Smith TJ, Fischer PR, Trehan I, Hiffler L, Arnold CD, Sitthideth D, Tancredi DJ, Schick MA, Yeh J, Stein-Wexler R, McBeth CN, Tan X, Nhiacha K, Kounnavong S. Establishing a case definition of thiamine responsive disorders among infants and young children in Lao PDR: protocol for a prospective cohort study. BMJ Open. 2020 Feb 13;10(2):e036539. doi: 10.1136/bmjopen-2019-036539.

  PMID: 32060165 BACKGROUND

• Smith TJ, Tan X, Arnold CD, Sitthideth D, Kounnavong S, Hess SY. Traditional prenatal and postpartum food restrictions among women in northern Lao PDR. Matern Child Nutr. 2022 Jan;18(1):e13273. doi: 10.1111/mcn.13273. Epub 2021 Sep 30.

  PMID: 34595830 BACKGROUND

• Hess SY, Arnold CD, Smith TJ, Allen LH, Hampel D, Jones KS, Parkington DA, Meadows SR, Sitthideth D, Kounnavong S. Thiamine Concentration in Human Milk Is Correlated With Maternal and Infant Thiamine Status: A Cross-Sectional Analysis of the Lao Thiamine Study. Matern Child Nutr. 2025 Jul;21(3):e70027. doi: 10.1111/mcn.70027. Epub 2025 Apr 10.

  PMID: 40211576 DERIVED

• Hess SY, Smith TJ, Arnold CD, Jones KS, Hampel D, Hiffler L, Trehan I, Fischer PR, Meadows SR, Parkington DA, Brown KH, Sitthideth D, Tan X, Koulman A, Allen LH, Kounnavong S. Assessment of Erythrocyte Transketolase, Whole Blood Thiamine Diphosphate, and Human Milk Thiamine Concentrations to Identify Infants and Young Children Responding Favorably to Therapeutic Thiamine Administration: Findings from the Lao Thiamine Study, a Prospective Cohort Study. Curr Dev Nutr. 2024 May 23;8(6):103786. doi: 10.1016/j.cdnut.2024.103786. eCollection 2024 Jun.

  PMID: 38974350 DERIVED

• Smith TJ, Arnold CD, Fischer PR, Trehan I, Hiffler L, Sitthideth D, Stein-Wexler R, Yeh J, Jones KS, Hampel D, Tancredi DJ, Schick MA, McBeth CN, Tan X, Allen LH, Sayasone S, Kounnavong S, Hess SY. A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic. J Pediatr. 2024 May;268:113961. doi: 10.1016/j.jpeds.2024.113961. Epub 2024 Feb 17.

  PMID: 38369233 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, plasma and erythrocyte samples will be collected among children. Blood, plasma, erythrocyte and breastmilk samples will be collected among their mothers.

MeSH Terms

Conditions

Thiamine Deficiency

Interventions

Thiamine; Standard of Care

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; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Sengchanh Kounnavong, MD, PhD

  Lao Tropical and Public Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: August 13, 2018
• Study Start: June 17, 2019
• Primary Completion: February 25, 2021
• Study Completion: February 25, 2021
• Last Updated: August 15, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 3 years after completion of data collection

Locations

LA (1)