Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03616288
Other study ID # MSVUREB2017-141
Secondary ID 112NECHR
Status Completed
Phase N/A
First received
Last updated
Start date August 28, 2018
Est. completion date January 28, 2021

Study information

Verified date February 2021
Source Mount Saint Vincent University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

(see full protocol)


Recruitment information / eligibility

Status Completed
Enrollment 335
Est. completion date January 28, 2021
Est. primary completion date May 5, 2020
Accepts healthy volunteers No
Gender Female
Age group 18 Years to 45 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
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).

Locations

Country Name City State
Cambodia Helen Keller International Kampong Thom Kapmong Thom Province

Sponsors (9)

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

Country where clinical trial is conducted

Cambodia, 

Outcome

Type Measure Description Time frame Safety issue
Other Infant thiamine diphosphate concentrations (ThDP) To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases infant thiamine diphosphate concentrations (ThDP) 24 weeks postnatally, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder. 24 weeks postnatal
Other Human milk total thiamine concentrations 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 4 and 12 weeks postpartum. 4 and 12 weeks postpartum
Other Infant transketolase activity To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases infant transketolase activity at 24 weeks postnatally, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder. 24 weeks postnatal
Other Maternal ThDP (dose response) To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases maternal ThDP at 24 weeks postpartum, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder. 24 weeks postpartum
Other Maternal transketolase activity (dose response) To estimate the dose on the dose response curve where additional maternal intake of thiamine (oral dose) no longer meaningfully increases maternal ETKac at 24 weeks postpartum, and assess whether this depends on the presence/absence of a genetic hemoglobin disorder. 24 weeks postpartum
Other Human milk total thiamine concentrations To test for differences between the 4 randomized groups on human milk total thiamine at 4, 12, and 24 weeks postpartum. 4, 12, and 24 weeks postpartum
Other Maternal ThDP (by arm) To test for differences between the 4 randomized groups on maternal ThDP at 24 weeks postpartum, and assess whether this depends on the presence/absence of genetic hemoglobin disorder. 24 weeks postpartum
Other Maternal transketolase activity (by arm) To test for differences between the 4 randomized groups on maternal ETKac at 24 weeks postpartum and assess whether this depends on the presence/absence of a genetic hemoglobin disorder. 24 weeks postpartum
Other Household salt intake To estimate usual household salt intake from mean fortnightly salt disappearance (weight lost, in g). within 2 and 24 weeks postpartum
Other Salt intake of household members To estimate salt intake among a subset of 100 lactating women, their male partners (if applicable), and their children 24-59 months (if applicable) using observed weighed salt intake records. within 2 and 24 weeks postpartum
Other Sodium intake of women To estimate sodium intake using 24 hr urinary sodium concentrations among a subset of 100 lactating women. within 2 and 24 weeks postpartum
Other Mullen scores To test for differences between the 0 & 10 mg randomized groups on Composite Mullen and the 5 subscales of the Mullen at 24 and 52 weeks postnatally.
Score notes for Mullen Scales of Early Learning
Gross Motor Scale: Raw score range: 0-36 (higher scores reflect better performance) Visual Reception Scale: Raw score range: 0-50 (higher scores reflect better performance) Fine Motor Scale: Raw score range: 0-49 (higher scores reflect better performance) Receptive Language Scale: Raw score range: 0-48 (higher scores reflect better performance) Expressive Language Scale: Raw score range: 0-50 (higher scores reflect better performance)
All raw scores are converted to age-adjusted T-scores (provided by manual).
An optional Early Learning Composite Score can be calculated by summing the T-scores of all but the Gross Motor Scale.
24 and 52 weeks postnatal
Other Visual paired comparison To test for differences between the 0 & 10 mg randomized groups on Visual Paired Comparison Novelty Score and the attention and processing speed subscales at 24 and 52 weeks postnatally.
Score notes for Visual Paired Comparison task
Scale ranges: An overall novelty score is calculated that averages across all face and pattern trials, and is a percentage reflecting the percent of time infants' looked at the novel item during the test phase, calculated as the duration looking to the novel item divided by the sum of the duration of looking to the novel item plus the duration looking to the familiar item.
Sub-scales: Two sub-scales are calculated: the novelty score averaged across face trials, and the novelty score averaged across pattern trials. The total scale composite averages the novelty score across the two sub-scales.
For all scales, he range is 0-100%, and higher novelty scores indicate better outcomes.
24 and 52 weeks postnatal
Other Language Preference Task To test for differences between the 0 & 10 mg randomized groups on the Language Preference Task Score at 24 weeks postnatally. 24 weeks postnatal
Other Oculomotor scores To test for differences between 0 & 10 mg randomized groups on oculomotor scores at 24 weeks postnatally.
Score notes for the Oculomotor Test:
The proposed oculomotor test is not a single, published instrument, but instead, combines several standard screening items.
Strabismus: absent or present; score: 0-1 Nystagmus: absent or present; score: 0-1 Amblyopia: absent or present; score 0-1
Saccade:
guided saccade: absent or present; score 0-1
scanning: absent or present; score 0-1
predicted saccade: absent or present; score 0-1
Smooth pursuit:
overall pursuit: absent or present; score 0-1
horizontal pursuit: score 0-1
vertical pursuit: score 0-1
Total oculomotor score (optional): sum of all scored exam items: range 0-9
24 weeks postnatal
Other Inflammation To determine the effect of inflammation, as measured by C-reactive protein (CRP) and a-1-acid-glycoprotein (AGP) on maternal ThDP at 2 and 24 weeks postpartum, and infant ThDP at 24 weeks postnatal. 24 weeks postnatal
Primary 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
See also
  Status Clinical Trial Phase
Completed NCT03550794 - Thiamine as a Renal Protective Agent in Septic Shock Phase 2
Completed NCT03263442 - High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation Phase 2
Completed NCT05663164 - Effect of Thiamine on Serum Glucagon And Reactive Oxygen Species (ROS) N/A
Withdrawn NCT03122678 - Thiamine Supplementation in Patients With Septic Shock Phase 1
Completed NCT04641104 - The Thiamine Administration After Cardiac Surgery Trial Phase 4
Recruiting NCT06298344 - The Role of Thiamine After Transcatheter Closure in Children With Left-to-Right Shunt Congenital Heart Disease Early Phase 1
Completed NCT03626337 - Thiamine Responsive Disorders (TRD) Among Infants in Lao PDR
Completed NCT05390086 - Further Development and Assessment of Tools to Measure Risk Factors for and Treatment of Thiamine Deficiency Disorders
Recruiting NCT05480943 - Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans
Active, not recruiting NCT04453761 - Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass Phase 4
Completed NCT03746106 - The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine Phase 4
Completed NCT03554668 - Systemic Inflammatory Response: Thiamine and Magnesium Status (Sir TaM Study)
Completed NCT01524315 - Preoperative Parenteral Thiamine Supplementation in Patients Undergoing Heart Surgery Phase 4
Completed NCT02464865 - Thiamin Deficiency in Obese Thai Children Phase 4
Completed NCT03228030 - Thiamine Supplementation in Heart Failure: a Pilot Randomized Controlled Crossover Trial Phase 1