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Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR

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ClinicalTrials.gov Identifier: NCT03626337
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : June 26, 2019
Sponsor:
Collaborator:
Lao Tropical and Public Health Institute
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:
A hospital- and community-based study in Luang Prabang, Lao PDR, which will include a group of hospitalized children 21 days to <12 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.

Condition or disease Intervention/treatment
Thiamine Deficiency Drug: Thiamine 100 MG/ML

Detailed Description:

The study will address the following questions:

  • Among infants with symptoms consistent with thiamine deficiency disorder (TDD), which clinical symptoms and risk factors distinguish those who respond positively to thiamine administration from those who do not respond?
  • Among young infants, which biomarkers of thiamine status and cut-offs of these biomarkers are associated with thiamine responsive disorder?

To answer the first question, the investigators will develop and validate clinical prediction models that will use clinical signs and risk factors that can be reliably measured early in patients diagnosed with suspected thiamine deficiency to predict which patients would respond favorably to thiamine supplementation. Such validated clinical prediction rules would be of value in making thiamine treatment decisions and in identifying patient characteristics with prognostic significance. To answer the second question, investigators will contrast TRD responders to hospitalized non-TRD infants and to a community-based control group, to compare the distribution of patient characteristics, other risk factors (exposures) and biomarkers of thiamine status. The investigators will also develop multiple logistic regression models that use selected patient characteristics and exposures. These results would identify characteristics that may more clearly distinguish individuals that have TDD-like symptoms that would respond favorably to thiamine supplementation from individuals in the same community who do not have TDD-like symptoms. These characteristics may be of value in targeting thiamine screening and supplementation efforts in low-resource settings.

Infants in the target age range, who are admitted to the participating hospital, will be screened by hospital 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 infants who would respond clinically to thiamine administration to correct the deficiency. If a child is in the target age range (21 days to <12 months) meets any one of the inclusion criteria, parental consent will be obtained and infants 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, namely 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 infants and infants 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.


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Study Type : Observational
Estimated Enrollment : 927 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: A Study to Establish a Case Definition of Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : June 16, 2020
Estimated Study Completion Date : June 16, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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
100 mg thiamine provided as intramuscular injection
Other Name: Standard of care

Community-based cohort
Sex-, age- and regionally matched control group



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Biomarkers of whole blood thiamine diphosphate (ThDP) and erythrocyte transketolase activity coefficient (ETKac) [ Time Frame: Baseline ]
    Associations between ThDP and ETKac with TRD will be determined and appropriate cut-offs of these biomarkers suggesting TRD will be proposed


Biospecimen Retention:   Samples Without DNA
Blood, plasma and erythrocyte samples will be collected among infants. Blood, plasma, erythrocyte and breastmilk samples will be collected among their mothers.


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 11 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Hospitalized infants:

Infants in the target age range (21 days to <12 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 control group will be enrolled based on the characteristics of the hospitalized group.

Mothers of all participating infants will be invited to the study.

Criteria

Inclusion criteria of hospital-based infants:

  • 21 days to <12 months and admitted to 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 (>50/min for 2-12 mo; > 60/min for 3-8 wks)
  • 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

Exclusion criteria of hospital-based infants:

  • None

Inclusion criteria of community-based infants, who will be sex- and age-matched (within one month) to hospital-based participants :

  • Infants aged 21 days to <12 months
  • Residing in selected communities

Exclusion criteria of community-based infants:

- Severe acute illness warranting immediate hospital referral

Inclusion criteria of participants' mothers:

- Mother of hospital-based study participant or community-based study participant

Exclusion criteria of participants' mothers:

  • Severe acute illness warranting immediate hospital referral
  • Unable to provide informed consent due to reduced decision making ability

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03626337


Contacts
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Contact: Sonja Y Hess, PhD 530 752 1992 syhess@ucdavis.edu

Locations
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Lao People's Democratic Republic
Lao Friends Hospital for Children Recruiting
Luang Prabang, Lao People's Democratic Republic
Contact: Indi Trehan, MD       executivedirector@fwablaos.org   
Sponsors and Collaborators
University of California, Davis
Lao Tropical and Public Health Institute
Investigators
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Principal Investigator: Sengchanh Kounnavong, MD, PhD Lao Tropical and Public Health Institute

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03626337     History of Changes
Other Study ID Numbers: 1329444
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: June 26, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The complete de-identified dataset will be made publically available. Associated data dictionaries will be made available along with the datasets.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Within 3 years after completion of data collection

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Thiamine Deficiency
Beriberi
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Thiamine
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs