Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial
Introduction Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potenti...
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BMJ Publishing Group
2019-07-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/9/7/e029255.full |
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| author | Kyly C Whitfield Hou Kroeun Tim Green Frank T Wieringa Mam Borath Prak Sophonneary Jeffrey R Measelle Dare Baldwin Lisa N Yelland Shalem Leemaqz Kathleen Chan Jelisa Gallant |
| author_facet | Kyly C Whitfield Hou Kroeun Tim Green Frank T Wieringa Mam Borath Prak Sophonneary Jeffrey R Measelle Dare Baldwin Lisa N Yelland Shalem Leemaqz Kathleen Chan Jelisa Gallant |
| author_sort | Kyly C Whitfield |
| collection | DOAJ |
| description | Introduction Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown.Methods and analysis In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of Emax dose–response curves will be estimated using non-linear least squares models with both ‘intention to treat’ and a secondary ‘per-protocol’ (capsule compliance ≥80%) analyses.Ethics and dissemination Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017–141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants’ communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations.Trial registration number NCT03616288. |
| format | Article |
| id | doaj-art-68bb5f70713e473c8bc406b7b8d788da |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2019-07-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-68bb5f70713e473c8bc406b7b8d788da2025-08-20T02:50:29ZengBMJ Publishing GroupBMJ Open2044-60552019-07-019710.1136/bmjopen-2019-029255Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trialKyly C Whitfield0Hou Kroeun1Tim Green2Frank T Wieringa3Mam Borath4Prak Sophonneary5Jeffrey R Measelle6Dare Baldwin7Lisa N Yelland8Shalem Leemaqz9Kathleen Chan10Jelisa Gallant11Mount Saint Vincent University, Halifax, Nova Scotia, CanadaHelen Keller International Cambodia, Phnom Penh, CambodiaWomen and Kids Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaInstitut de Recherche pour le Développement (IRD), Montpellier, FranceNational Sub-Committee for Food Fortification, Cambodia Ministry of Planning, Phnom Penh, CambodiaNational Nutrition Programme, Maternal and Child Health Centre, Cambodia Ministry of Health, Phnom Penh, CambodiaDepartment of Psychology, University of Oregon, Eugene, Oregon, USADepartment of Psychology, University of Oregon, Eugene, Oregon, USASAHMRI Women and Kids, South Australian Health and Medical Research Institute, North Adelaide, South Australia, AustraliaSouth Australian Health & Medical Research Institute, Adelaide, AustraliaMount Saint Vincent University, Halifax, Nova Scotia, CanadaMount Saint Vincent University, Halifax, Nova Scotia, CanadaIntroduction Thiamine (vitamin B1) deficiency remains a concern in Cambodia where women with low thiamine intake produce thiamine-poor milk, putting their breastfed infants at risk of impaired cognitive development and potentially fatal infantile beriberi. Thiamine fortification of salt is a potentially low-cost, passive means of combating thiamine deficiency; however, both the dose of thiamine required to optimise milk thiamine concentrations as well as usual salt intake of lactating women are unknown.Methods and analysis In this community-based randomised controlled trial, 320 lactating women from Kampong Thom, Cambodia will be randomised to one of four groups to consume one capsule daily containing 0, 1.2, 2.4 or 10 mg thiamine as thiamine hydrochloride, between 2 and 24 weeks postnatal. The primary objective is to estimate the dose where additional maternal intake of thiamine no longer meaningfully increases infant thiamine diphosphate concentrations 24 weeks postnatally. At 2, 12 and 24 weeks, we will collect sociodemographic, nutrition and health information, a battery of cognitive assessments, maternal (2 and 24 weeks) and infant (24 weeks only) venous blood samples (biomarkers: ThDP and transketolase activity) and human milk samples (also at 4 weeks; biomarker: milk thiamine concentrations). All participants and their families will consume study-provided salt ad libitum throughout the trial, and we will measure salt disappearance each fortnight. Repeat weighed salt intakes and urinary sodium concentrations will be measured among a subset of 100 participants. Parameters of Emax dose–response curves will be estimated using non-linear least squares models with both ‘intention to treat’ and a secondary ‘per-protocol’ (capsule compliance ≥80%) analyses.Ethics and dissemination Ethical approval was obtained in Cambodia (National Ethics Committee for Health Research 112/250NECHR), Canada (Mount Saint Vincent University Research Ethics Board 2017–141) and the USA (University of Oregon Institutional Review Board 07052018.008). Results will be shared with participants’ communities, as well as relevant government and scientific stakeholders via presentations, academic manuscripts and consultations.Trial registration number NCT03616288.https://bmjopen.bmj.com/content/9/7/e029255.full |
| spellingShingle | Kyly C Whitfield Hou Kroeun Tim Green Frank T Wieringa Mam Borath Prak Sophonneary Jeffrey R Measelle Dare Baldwin Lisa N Yelland Shalem Leemaqz Kathleen Chan Jelisa Gallant Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial BMJ Open |
| title | Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial |
| title_full | Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial |
| title_fullStr | Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial |
| title_full_unstemmed | Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial |
| title_short | Thiamine dose response in human milk with supplementation among lactating women in Cambodia: study protocol for a double-blind, four-parallel arm randomised controlled trial |
| title_sort | thiamine dose response in human milk with supplementation among lactating women in cambodia study protocol for a double blind four parallel arm randomised controlled trial |
| url | https://bmjopen.bmj.com/content/9/7/e029255.full |
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