Early Life Thiamine Study
Early Life Thiamine Supplementation for Infant Neurocognitive Benefits: a Randomized Controlled Trial
Thiamine (vitamin B1) is an important nutrient needed for energy metabolism, brain development, and overall health. However, low thiamine intake is a concern in countries where white rice is the main staple since it contains little thiamine. If pregnant or breastfeeding women do not eat enough thiamine, their babies may also become deficient. Severe thiamine deficiency can cause beriberi, which can be life-threatening. Milder deficiency during early life may affect brain development.
Healthy pregnant women should eat 1.4 mg thiamine daily. In a previous study in rural Cambodia, study investigators found that giving breastfeeding mothers a higher dose of thiamine (10mg per day) improved their infants' brain development at six months of age. However, supplementation began two weeks after birth. Since much of an infant's brain development occurs in utero, starting mother's supplementation earlier - in pregnancy - may provide greater benefits.
Study investigators are now conducting a study with pregnant women in Cambodia. Participants will receive either the usual amount of thiamine found in multiple micronutrient supplements or a higher dose, beginning in pregnancy and continuing until their child is 18 months old. The primary outcome is cognition at 18 months, to see whether higher thiamine intake during pregnancy and early childhood leads to measurable improvements in early brain development.
調査の概要
状態
条件
詳細な説明
Please see attached study protocol for full details.
Background:
Thiamine (vitamin B1) is an essential micronutrient crucial for normal physiological functioning and healthy child development. Thiamine requirements increase with carbohydrate-rich diets (e.g. white rice) and during periods of high metabolism (e.g. perinatal women, infancy). The limited data available show that the prevalence of thiamine deficiency is high in women of childbearing age and their infants in several low- and middle-income settings, notably in South and Southeast Asia, where white rice is the dietary staple, but also in several African countries. Thiamine-deficient pregnant and lactating women produce breastmilk low in thiamine, putting their breastfed infants at risk of deficiency, and potentially fatal beriberi. In addition, recent evidence suggests that sub-clinical thiamine deficiency may be conferred prenatally, placing millions of infants at risk of neurocognitive deficits, undercutting life-long well-being and productivity.
Preliminary Data:
In coordination with the Cambodian Ministry of Health, study investigators undertook a four-parallel-arm, randomized, controlled trial (NCT03616288) in rural Cambodia to estimate the dose of maternal thiamine required postpartum to optimize breastmilk thiamine concentrations; secondary exploratory outcomes included neurocognitive assessments. Mothers were randomized to consume 0, 1.2, 2.4, or 10 mg daily thiamine from 2 weeks through 6 months postnatal. While milk thiamine concentrations were significantly higher in all thiamine groups compared to placebo, critically, at 6 months postnatal, only infants in the 10 mg/d group showed robust neurocognitive benefits. Additionally, infants whose mothers had higher milk thiamine concentrations at our pre-supplementation baseline (2 weeks postpartum) showed significantly improved neurocognitive outcomes at 6 months postnatal, suggesting that infants' prenatal access to adequate thiamine may have critical benefits for neurocognitive development.
Research Gap:
The prior trial indicated that 10 mg/d maternal thiamine supplementation, higher than current recommendations, was needed to support infant neurocognitive development in several domains. However, supplementation started at 2 weeks postpartum. Given how much foundational neurodevelopment occurs from conception through infancy, earlier and longer thiamine supplementation -- starting in pregnancy and maintained through 18 months postnatal -- is likely to further support neurocognitive development.
Design:
This will be a two parallel-arm, double-blind randomized controlled trial to compare the standard dose of thiamine in multiple micronutrient supplements throughout the perinatal and early childhood periods to a higher thiamine dose. Our primary outcome is infant neurocognitive development (Mullen Scales of Early Learning Early Learning Composite, MSEL-ELC) at 18 months postnatal. Secondary neurocognitive outcomes include the MSEL sub-scales, Global Scales of Early Development (GSED), and Visual Paired-Comparison Task (VPC), at 18 months postnatal.
Sample Size:
To detect a mean difference in 3 points in MSEL scores with 90% power (d=0.16, two-tailed α=0.05), and accounting for 20% losses, this study will require N=1,972 participants, 986 per group, to detect the main effect on the primary outcome, MSEL-ELC, at 18 months postnatal.
Statistical Analysis for Primary Outcome:
Scores on MSEL-ELC at 18 months will be compared between groups using a linear-regression model, with adjustment for health center, gestational age at enrolment, and birth anthropometry, and using generalized estimating equations with an independence working-correlation structure to account for multiple births. The effect of treatment will be described as a mean difference with a 95% CI. In all analyses, missing outcome data will be addressed using multiple imputation, performed separately by randomized group using chained equations. Outcomes will be analyzed on an intention-to-treat basis.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Kyly C Whitfield
- 電話番号：902-457-5978
- メール：kyly.whitfield@msvu.ca
研究場所
-
-
-
Kampong Thom、カンボジア
- 募集
- Community-based study
-
コンタクト：
- Hou Kroeun, Country Director, Helen Keller International
- 電話番号：+855 10 467 297
- メール：hkroeun@hki.org
-
-
参加基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
This community-based trial will take place in villages throughout Kampong Thom province, Cambodia. Using convenience sampling, pregnant women (either primi- or multi-gravida) will be recruited from antenatal care programs within local health centers in Kampong Thom province.
Inclusion Criteria:
- women aged 18-45 years
- 12(+0) to 15(+6) weeks pregnant, based on last menstrual period
- planning to breastfeed for at least 6 months
Exclusion Criteria:
- consumed thiamine-containing supplements in the preceding 3 months
- planning on moving out of province in the next year
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
プラセボコンパレーター：Standard of Care +
multiple micronutrient supplement formulations containing the RNI for thiamine: 1.4 mg/d for pregnant/lactating women (from 12-16 weeks pregnancy through 6 months postnatal), and 0.5 mg/d for children (6-18 months postnatal)
|
Standard of Care+ group From 12-16 weeks gestation through to 6 months postnatal, women will consume tablets orally. Starting at 6 months postnatal, supplements will then be administered directly to infants as daily liquid supplement drops. Details of supplement contents are found in the full protocol. Multiple micronutrient supplements will include the standard 15 micronutrients included in the United Nations International Multiple Micronutrient Antenatal Preparation Multiple Micronutrient Supplements (UNIMAPP MMS) formulation, which are the same found in standard micronutrient powders designed for children 6-24 months: thiamine, as well as vitamins A, D, E, K, C, B2, B3, B6, B12, folic acid, iodine, zinc, selenium, and copper. "Standard of Care +" and "High thiamine MMS" groups will take supplements that are identical except for thiamine content. Women: 1.4 mg thiamine Children: 0.5 mg thiamine High thiamine MMS group From 12-16 weeks gestation through to 6 months postnatal, women will consume tablets orally. Starting at 6 months postnatal, supplements will then be administered directly to infants as daily liquid supplement drops. Details of supplement contents are found in the full protocol. Multiple micronutrient supplements will include the standard 15 micronutrients included in the United Nations International Multiple Micronutrient Antenatal Preparation Multiple Micronutrient Supplements (UNIMAPP MMS) formulation, which are the same found in standard micronutrient powders designed for children 6-24 months: thiamine, as well as vitamins A, D, E, K, C, B2, B3, B6, B12, folic acid, iodine, zinc, selenium, and copper. "Standard of Care +" and "High thiamine MMS" groups will take supplements that are identical except for thiamine content. Women: 10 mg thiamine Children: 5 mg thiamine |
|
実験的：High-thiamine MMS
multiple micronutrient supplement formulations containing a higher dose of daily thiamine: 10 mg/d for pregnant/lactating women (12-16 weeks pregnancy through 6 months postnatal), and 5 mg/d for children (6-18 months postnatal)
|
Standard of Care+ group From 12-16 weeks gestation through to 6 months postnatal, women will consume tablets orally. Starting at 6 months postnatal, supplements will then be administered directly to infants as daily liquid supplement drops. Details of supplement contents are found in the full protocol. Multiple micronutrient supplements will include the standard 15 micronutrients included in the United Nations International Multiple Micronutrient Antenatal Preparation Multiple Micronutrient Supplements (UNIMAPP MMS) formulation, which are the same found in standard micronutrient powders designed for children 6-24 months: thiamine, as well as vitamins A, D, E, K, C, B2, B3, B6, B12, folic acid, iodine, zinc, selenium, and copper. "Standard of Care +" and "High thiamine MMS" groups will take supplements that are identical except for thiamine content. Women: 1.4 mg thiamine Children: 0.5 mg thiamine High thiamine MMS group From 12-16 weeks gestation through to 6 months postnatal, women will consume tablets orally. Starting at 6 months postnatal, supplements will then be administered directly to infants as daily liquid supplement drops. Details of supplement contents are found in the full protocol. Multiple micronutrient supplements will include the standard 15 micronutrients included in the United Nations International Multiple Micronutrient Antenatal Preparation Multiple Micronutrient Supplements (UNIMAPP MMS) formulation, which are the same found in standard micronutrient powders designed for children 6-24 months: thiamine, as well as vitamins A, D, E, K, C, B2, B3, B6, B12, folic acid, iodine, zinc, selenium, and copper. "Standard of Care +" and "High thiamine MMS" groups will take supplements that are identical except for thiamine content. Women: 10 mg thiamine Children: 5 mg thiamine |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mullen's Scales of Early Learning "Early Learning Composite" T-score (MSEL-ELC)
時間枠：18 months postnatal
|
Early Learning Composite (ELC) Standard Score is derived from the sum of the age adjusted T-scores for all but the Gross Motor scales: ELC Standard Score = Visual Reception T-Score + Fine Motor T-Score + Receptive Language T-Score + Expressive Language T-Score ELC Standard Score Mean = 100 ELC Standard Score SD = 15 ELC Standard Score Range (Min/Max) = 49 to 155 |
18 months postnatal
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mullen's Scales of Early Learning "Early Learning Composite" T-score (MSEL-ELC)
時間枠：2 weeks and 6 months postnatal
|
Early Learning Composite (ELC) Standard Score is derived from the sum of the age adjusted T-scores for all but the Gross Motor scales: ELC Standard Score = Visual Reception T-Score + Fine Motor T-Score + Receptive Language T-Score + Expressive Language T-Score ELC Standard Score Mean = 100 ELC Standard Score SD = 15 ELC Standard Score Range (Min/Max) = 49 to 155 |
2 weeks and 6 months postnatal
|
|
Mullen's Scales of Early Learning sub-scales
時間枠：2 weeks, 6 months, and 18 months postnatal
|
The five MSEL sub-scales are: Gross Motor, Fine Motor, Visual Reception, Receptive Language, and Expressive Language. Minimum and maximum values (Raw Scores) Gross Motor: 0 to 36 Visual Reception: 0 to 50 Fine Motor: 0 to 49 Receptive Language: 0 to 48 Expressive Language: 0 to 50 Age adjusted T-Scores are derived from the raw scores for each scale and range from: Min = 20 Max = 80 Mean T-Score = 50 (SD = 10) |
2 weeks, 6 months, and 18 months postnatal
|
|
Global Scales of Early Development (GSED)
時間枠：2 weeks, 6 months, and 18 months postnatal
|
Caregiver-report.
World Health Organization published scoring guide available at: https://iris.who.int/bitstream/handle/10665/366272/WHO-MSD-GSEDpackage-v1.0-2023.8-eng.pdf
|
2 weeks, 6 months, and 18 months postnatal
|
|
Visual Paired-Comparison (VPC) Task
時間枠：18 months postnatal
|
18 months postnatal
|
|
|
Erythrocyte transketolase activity coefficient (ETKac)
時間枠：enrolment, 6 and 18 months
|
ETKac is a functional measure of thiamine status.
ETKac will be assessed in a sub-sample of n=210 participants.
Venous blood will be collected from mothers at baseline (12-16 weeks gestation) and their children at 6 months and 18 months postnatal.
|
enrolment, 6 and 18 months
|
|
Human milk thiamine concentrations
時間枠：2 weeks, 6 months, and 18 months postnatal
|
Human milk thiamine concentrations will be assessed in a sub-sample of n=210 participants.
Full breast expressions will be collected from mothers at 2 weeks, 6 months, and 18 months postnatal.
|
2 weeks, 6 months, and 18 months postnatal
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- MSVU-REB-2025-234
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。