Thiamine DeficiencyNCT03626337
Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
An observational study of Thiamine Deficiency, run by University of California, Davis at 1 site in Laos.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 days to 17 monthsHealthy volunteers can take part
- Conditions the study is for
- Thiamine Deficiency
- What is being tested?
- Thiamine 100 MG/ML
- Type of treatment
- Injection or infusion
- How many people
- 1,394 participants
- Where
- 1 siteLaos
- Study dates
- 17 Jun 2019to 25 Feb 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 days to 17 months
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- 21 days to <18 months and seeking care at the collaborating hospital and meeting at least one of the following inclusion criteria:
- 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%)
Show all 18Show fewer
- 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
- Acute paralysis / flaccid paralysis
- Mother of hospital-based study participant or community-based study participant
Who cannot join
- None
- Inclusion criteria of community-based children, who will be frequency-matched based on sex, age and residence to hospital-based participants :
- Children aged 21 days to <18 months
- Residing in selected communities
- Severe acute illness warranting immediate hospital referral
- Severe acute illness warranting immediate hospital referral
- Unable to provide informed consent due to reduced decision making ability
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study to Establish a Case Definition of Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
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.
Read the detailed description
The study's primary objective is the development of a case definition for TRD among infants and young children with symptoms consistent with TDD, with the case definition being based on those clinical symptoms and other predictors that we find are better able to distinguish those who respond positively to thiamine administration from those who do not respond. As diagnostic tools available to treating physicians may differ by setting, we will repeat analyses after excluding from the set of candidate predictors those that are derived from assessments only available in higher-resource settings, such as laboratory biomarkers and ultrasonography.
A secondary objective is to fill the knowledge gap surrounding biomarkers of thiamine status in at-risk populations. Biomarker cut-offs for TRD will be developed in the hospital cohort and distributions will be characterised in both the hospital and community cohorts. The performance of our proposed cut-off will be compared to the performance of existing literature cut-offs.
Additionally, all identified predictors and biomarker cut-offs will be compared across the community cohort, non-TRD hospital cohort, and TRD hospital cohort to assess the prevalence of risk factors among apparently healthy infants and young children and assess the usefulness of the TRD case definition in various settings.
Infants and children in the target age range, who are seeking care at the collaborating hospital, will be screened by study staff to determine the presence of any of the inclusion criteria. The list of inclusion criteria has been developed based on a broad range of TDD-compatible symptoms to reduce the risk of potentially missing children who would respond clinically to thiamine administration to correct the deficiency. If a child is in the target age range (21 days to <18 months) meets any one of the inclusion criteria, parental consent will be obtained and children will be referred to a study physician for a detailed physical exam. An echocardiogram and cranial ultrasound will be performed to explore the complete range of TDD complications. A venous blood sample will be obtained by venipuncture for assessment of indicators of thiamine status. The data collection will follow a structured timeline after the first thiamine dose has been administered. In particular, the thiamine administration will be defined as hour zero, and the above described physical exam will be repeated 4, 8, 12, 24, 36, 48, and 72 hours after the initial thiamine administration
Blood samples will be analyzed for whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac), inflammation and cardiac biomarkers and for a complete blood count (CBC). The purpose of determining these indicators is to better describe the TRD cases and explore differences between TRD cases, non-TRD children and children in the community, with the ultimate goal that these indicators may be useful for screening in the future. Moreover, to determine the association between TRD and maternal thiamine status as a potential risk factor, investigators will collect a blood sample from infants's mothers to assess maternal thiamine status, and among breast feeding mothers a breastmilk sample for assessment of thiamine concentration.
- Conditions
- Thiamine Deficiency
- Being tested
- Thiamine 100 MG/ML
- Medical subject headings
- Thiamine Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiamine 100 MG/MLDrug
Also called Standard of care
100 mg thiamine provided as intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| Hospital-based cohort | 100 mg thiamine provided via intramuscular and/or intravenous injection (Thiamine 100 MG/ML) daily for 3 days Receives: Drug: Thiamine 100 MG/ML | |
| Community-based cohort | Sex-, age- and regionally matched comparison group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 48-72 hours
Secondary outcomes (2)
Biomarkers of whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac)
Associations between ThDP and ETKac with TRD will be determined and appropriate cut-offs of these biomarkers suggesting TRD will be proposed
Measured: Baseline
Hemoglobin and biomarkers of other micronutrients (ferritin, transferrin receptor, retinol binding protein, erythrocyte glutathione reductase activation coefficient (EGRAC)), and inflammation (CRP, AGP)
Nutrition and health status will be assessed to explore potential risk factors for TRD
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2018
- Study start17 Jun 2019
- Primary completion25 Feb 2021
- Study completion25 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Thiamine DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,394 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Lao Tropical and Public Health Institute
- Responsible party
- Sponsor
- Investigators
- Sengchanh Kounnavong, MD, PhD, Principal investigator, Lao Tropical and Public Health Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03626337
- Sponsor's protocol ID
- 1329444
- Status last verified
- Aug 2022
- First submitted
- 17 Jul 2018
- Last updated
- 15 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The complete de-identified dataset will be made publically available. Associated data dictionaries will be made available along with the datasets.
Publications
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.
PubMed 32060165Smith 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.
PubMed 34595830Hess 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.
PubMed 40211576Hess 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.
PubMed 38974350Smith 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.
PubMed 38369233Hess SY, Smith TJ, Sitthideth D, Arnold CD, Tan X, Jones KS, Brown KH, Alayon S, Kounnavong S. Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR. Matern Child Nutr. 2024 Jan;20(1):e13565. doi: 10.1111/mcn.13565. Epub 2023 Oct 6.
PubMed 37803889
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Establish a Case Definition of Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
- ClinicalTrials.gov ID
- NCT03626337
- Acronym / sponsor ID
- 1329444
- Conditions
- Thiamine Deficiency
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,394 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Lao Tropical and Public Health Institute
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- 25 Feb 2021 (actual)
- Study completion
- 25 Feb 2021 (actual)
- First posted
- 13 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The study's primary objective is the development of a case definition for TRD among infants and young children with symptoms consistent with TDD, with the case definition being based on those clinical symptoms and other predictors that we find are better able to distinguish those who respond positively to thiamine administration from those who do not respond. As diagnostic tools available to treating physicians may differ by setting, we will repeat analyses after excluding from the set of candidate predictors those that are derived from assessments only available in higher-resource settings, such as laboratory biomarkers and ultrasonography.
A secondary objective is to fill the knowledge gap surrounding biomarkers of thiamine status in at-risk populations. Biomarker cut-offs for TRD will be developed in the hospital cohort and distributions will be characterised in both the hospital and community cohorts. The performance of our proposed cut-off will be compared to the performance of existing literature cut-offs.
Additionally, all identified predictors and biomarker cut-offs will be compared across the community cohort, non-TRD hospital cohort, and TRD hospital cohort to assess the prevalence of risk factors among apparently healthy infants and young children and assess the usefulness of the TRD case definition in various settings.
Infants and children in the target age range, who are seeking care at the collaborating hospital, will be screened by study staff to determine the presence of any of the inclusion criteria. The list of inclusion criteria has been developed based on a broad range of TDD-compatible symptoms to reduce the risk of potentially missing children who would respond clinically to thiamine administration to correct the deficiency. If a child is in the target age range (21 days to <18 months) meets any one of the inclusion criteria, parental consent will be obtained and children will be referred to a study physician for a detailed physical exam. An echocardiogram and cranial ultrasound will be performed to explore the complete range of TDD complications. A venous blood sample will be obtained by venipuncture for assessment of indicators of thiamine status. The data collection will follow a structured timeline after the first thiamine dose has been administered. In particular, the thiamine administration will be defined as hour zero, and the above described physical exam will be repeated 4, 8, 12, 24, 36, 48, and 72 hours after the initial thiamine administration
Blood samples will be analyzed for whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac), inflammation and cardiac biomarkers and for a complete blood count (CBC). The purpose of determining these indicators is to better describe the TRD cases and explore differences between TRD cases, non-TRD children and children in the community, with the ultimate goal that these indicators may be useful for screening in the future. Moreover, to determine the association between TRD and maternal thiamine status as a potential risk factor, investigators will collect a blood sample from infants's mothers to assess maternal thiamine status, and among breast feeding mothers a breastmilk sample for assessment of thiamine concentration.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hospital-based cohort | – | Drug: Thiamine 100 MG/ML100 mg thiamine provided via intramuscular and/or intravenous injection (Thiamine 100 MG/ML) daily for 3 days |
| Community-based cohort | – | –Sex-, age- and regionally matched comparison group |
Who may qualify
- Ages
- 21 days to 17 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (18 listed)
- 21 days to <18 months and seeking care at the collaborating hospital and meeting at least one of the following inclusion criteria:
- 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)
Key exclusion criteria (7 listed)
- None
- Inclusion criteria of community-based children, who will be frequency-matched based on sex, age and residence to hospital-based participants :
- Children aged 21 days to <18 months
- Residing in selected communities
- Severe acute illness warranting immediate hospital referral
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thiamine 100 MG/MLAlso: Standard of care100 mg thiamine provided as intramuscular injection | Drug | Hospital-based cohort |
Primary outcome
Thiamine Responsive Disorder (TRD)
Time frame: 48-72 hours
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
2 secondary outcomes
Biomarkers of whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac)
Time frame: Baseline
Hemoglobin and biomarkers of other micronutrients (ferritin, transferrin receptor, retinol binding protein, erythrocyte glutathione reductase activation coefficient (EGRAC)), and inflammation (CRP, AGP)
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2022.
- Background: PubMed 32060165Hess 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.
- Background: PubMed 34595830Smith 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.
- Derived from this study: PubMed 40211576Hess 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.
- Derived from this study: PubMed 38974350Hess 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.
- Derived from this study: PubMed 38369233Smith 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.
- Derived from this study: PubMed 37803889Hess SY, Smith TJ, Sitthideth D, Arnold CD, Tan X, Jones KS, Brown KH, Alayon S, Kounnavong S. Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR. Matern Child Nutr. 2024 Jan;20(1):e13565. doi: 10.1111/mcn.13565. Epub 2023 Oct 6.
- Individual participant dataSharing planned: Yes. The complete de-identified dataset will be made publically available. Associated data dictionaries will be made available along with the datasets.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sengchanh Kounnavong, MD, PhD principal investigator
Lao Tropical and Public Health Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thiamine Deficiency, run by University of California, Davis at 1 site in Laos.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Laos. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Thiamine Responsive Disorder (TRD) (time frame: 48-72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03626337, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2022.