The OK Daily Study
Oral Vitamin K2 (Menaquinone-7; MK-7) Supplementation and Effect on Vitamin K Status of Breastfed Term Infants in Early Infancy; a Four-cohort Prospective, Part-randomised, Part-blinded Study.
The OK Daily Study is a multi-centred, part-randomised, part blinded, four cohort study. We are exploring daily dietary supplementation with vitamin K2, specifically menaquinone-7 (MK-7), given to breastfed infants or breastfeeding mothers to see whether this improves the incidence of biochemical vitamin K deficiency in the infants at 2 months postnatal age.
The overall aims are:
- To compare infant MK-7 supplementation with placebo
- To compare maternal MK-7 supplementation with placebo
- To compare infant MK-7 supplementation and maternal MK-7 supplementation
- To compare infant MK-7 supplementation with vitamin K1 supplementation via infant formula milk.
Once recruited, mother and infant pairs will be grouped initially based on the families' feeding choice. Breastfed infants will then be randomised 2:1 to the infant supplementation or maternal supplementation group. Within the infant supplementation group, infants will either receive MK-7 with vitamin D or a placebo containing vitamin D.
Follow up will occur at 2 months postnatal age (range 2-3 months postnatal age), where bloods and breastmilk samples will be collected to assess the infant and maternal vitamin K status.
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
The OK Daily Study is a multi-centre study taking place in the Norfolk and Norwich University Hospital, Norwich, UK, and Ashford and St Peters' Hospital, Chertsey, UK.
Infants born at ≥37 weeks' gestation will be recruited in the participating site if they meet eligibility criteria and are born within the recruitment window. Recruitment will take place before the mother and infant are discharged from the hospital following birth.
The two main arms of this study are breastfeeding and formula feeding. Mother and infant pairs will initially be allocated based on the family's feeding preferences.
Infants in the breastfeeding arm will be randomised into group 1 or group 2 in a 2:1 ratio. Group 1 allocation will be blinded; group 2 allocation will be open label.
- Group 1 - infant supplementation group. Infants will receive either 45 micrograms/day of MK-7 with 10 micrograms/day vitamin D3 or a placebo consisting of 10 micrograms/day vitamin D3
- Group 2 - maternal supplementation group. Mothers in this group will receive 2 mg/day MK-7. All breastfeeding infants in this group will receive 10 micrograms/day of vitamin D3.
Formula fed infants will be in group 3 and will not require any additional supplementation as part of this study. This is because infant formula is already supplemented with adequate amounts of vitamin K1 and vitamin D.
All supplements will be started within 7 days of birth. Vitamin D drops are included for breastfed infants as per national UK guidelines.
Follow up will be as follows:
1 month postnatal visit (range 1-1.5 months) - phone call.
o Confirmation of eligibility to continue, assessment of compliance with the intervention, and to schedule the in person follow up visit
2 months postnatal (range 2-3 months) - in person visit.
- All babies will have a single blood sample taken.
- Mothers who are in group 2 (mothers who have had MK-7 supplementation) and a selection of mothers from group 1 (breastfeeding mothers who are not supplemented with MK-7) will have a single blood sample taken and will be asked to provide a single breastmilk sample
- Mothers will be asked about their opinions on practising the supplementation.
Blood samples will be analysed for vitamin K status, including Proteins Induced by Vitamin K Absence/antagonism of prothrombin (PIVKA-II) and of osteocalcin (undercarboxylated osteocalcin), dephosphorylated-undercarboxylated matrix gla-protein (dp-ucMGP) and serum vitamin K concentrations (including of vitamin K1 and MK-7). Breastmilk samples will be analysed for vitamin K concentrations (including vitamin K1 and MK-7)
Once this in person follow up visit has been completed, the mother and baby pair will have completed the study.
Тип исследования
Регистрация (Оцененный)
Фаза
- Непригодный
Контакты и местонахождение
Контакты исследования
- Имя: Paul Professor Clarke
- Номер телефона: 01603 286286
- Электронная почта: PAUL.CLARKE@nnuh.nhs.uk
Учебное резервное копирование контактов
- Имя: Carianne Dr Lewis
- Электронная почта: Carianne.Lewis@nnuh.nhs.uk
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Ребенок
Принимает здоровых добровольцев
Описание
Inclusion Criteria:
- Infants, and mothers of infants, born ≥37 weeks gestational age
- Standard dose of intramuscular (IM) vitamin K prophylaxis given to the neonate following birth
- For breastfeeding mothers: the mother intends to exclusively/predominantly breastfeed their baby for at least 2 months
Exclusion Criteria:
- Inability or refusal to provide informed consent
- Inability to adhere to or comply with study procedures
- Babies who meet the inclusion gestation but would otherwise, as part of routine neonatal care, be provided with daily vitamin K drops (i.e. NeoKay drops) at discharge
- IM vitamin K prophylaxis not received at birth (parents declined vitamin K prophylaxis or parents chose for neonate to receive an oral course of vitamin K prophylaxis instead)
- Evidence of conjugated hyperbilirubinaemia (these babies are at higher risk of VKDB)
- Mothers, and babies born to mothers, who are taking any medication that could affect or antagonise vitamin K metabolism (i.e. warfarin, the anti-epileptic drugs phenytoin or carbamazepine, and cephalosporin, rifampicin and isoniazid antimicrobials)
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Профилактика
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Одинокий
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Другой: Mother and infant pairs who are breastfeeding.
Group 1 = infant supplementation group. Infants in this group will be randomised to receive either 6 drops a day containing 45 micrograms/day of MK-7 plus 10 micrograms/day vitamin D3 OR 10 micrograms/day vitamin D3 only (the active placebo, containing no vitamin K) Group 2 = maternal supplementation group. Mothers in this group will be given 2 mg/day MK-7 capsules. Infants in this group will receive 10 micrograms/day vitamin D3. |
6 drops/day providing 45 micrograms/day MK-7 plus 10 micrograms/day of vitamin D3
Другие имена:
6 drops/day providing 10 micrograms/day vitamin D3 and no supplementary MK-7.
Другие имена:
1 mg capsules of menaquinone-7, with a daily dose of 2 mg (i.e. 2 capsules per day)
|
|
Активный компаратор: Formula Feeding Infants
Infants who are exclusively formula feeding.
These infants will receive the recommended daily amount of vitamin K through their formula milk intake and so will not receive any additional vitamin K supplementation.
|
6 drops/day providing 10 micrograms/day vitamin D3 and no supplementary MK-7.
Другие имена:
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Comparison of the proportion of participants who have a PIVKA-II >0.05 AU/mL in the unsupplemented and supplemented infants.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
PIVKA-II = protein induced by vitamin K antagonism/absence; clotting protein II. Measured via serum blood sample in arbitrary units/mL. For the primary outcome, this is the comparison between the supplemented and unsupplemented infants. |
2 months postnatal age (range 2-3 months).
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Comparison of the proportion of participants who have a PIVKA-II >0.05 AU/mL in the various study groups.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
PIVKA-II = protein induced by vitamin K antagonism/absence; clotting protein II. Measured via serum blood sample in arbitrary units/mL. For secondary outcome, this is comparison between remaining groups, other than those assessed in the primary outcome measure. |
2 months postnatal age (range 2-3 months).
|
|
Comparison of serum levels of osteocalcin (undercarboxylated and carboxylated) between the study groups.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Both undercarboxylated and carboxylated levels of osteocalcin will be measured in nanograms/mL.
|
2 months postnatal age (range 2-3 months).
|
|
Comparison of the percentage of undercarboxylated osteocalcin as a proportion of total osteocalcin (%GluOC) between the study groups.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Total osteocalcin calculated by the sum of the undercarboxylated and carboxylated osteocalcin values.
|
2 months postnatal age (range 2-3 months).
|
|
Comparison of serum levels of dephosphorylated undercarboxylated matrix Gla Protein in included participants between the study groups.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Measured in picomol/mL
|
2 months postnatal age (range 2-3 months).
|
|
Comparison of levels of serum K vitamers (including, but no limited to, vitamin K1 and menaquinone-7) between the study groups.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Serum K vitamers will be reported in micrograms/mL.
|
2 months postnatal age (range 2-3 months).
|
|
Comparison of the levels of breastmilk K vitamers (including, but not limited to, vitamin K1 and menaquinone-7) between unsupplemented and supplemented mothers.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Serum K vitamers will be reported in nanograms/mL
|
2 months postnatal age (range 2-3 months).
|
|
Investigation of percentage compliance to study supplementation.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Amount of remaining supplement will be assessed at follow up.
This will then be used to calculate percentage compliance by comparing it to the expected volumes.
|
2 months postnatal age (range 2-3 months).
|
|
Investigation regarding families' opinions about infant and maternal vitamin supplementation.
Временное ограничение: 2 months postnatal age (range 2-3 months).
|
Measured via verbal questioning at follow up.
|
2 months postnatal age (range 2-3 months).
|
Соавторы и исследователи
Соавторы
Следователи
- Главный следователь: Paul Clarke, Professor, Norfolk and Norwich University Hospitals NHS Foundation Trust
Публикации и полезные ссылки
Общие публикации
- Schurgers LJ, Teunissen KJ, Hamulyak K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83. doi: 10.1182/blood-2006-08-040709. Epub 2006 Dec 7.
- Perrone S, De Bernardo G, Lembo C, Dell'Orto V, Giordano M, Beretta V, Petrolini C, Gambini L, Toni AL, Parigi G, Fontanarosa I, Natale MP, D'Amato G, Sordino D, Buonocore G. Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study. Eur J Clin Invest. 2024 Apr;54(4):e14141. doi: 10.1111/eci.14141. Epub 2023 Dec 9.
- Clarke P, Shearer MJ, Card DJ, Nichols A, Ponnusamy V, Mahaveer A, Voong K, Dockery K, Holland N, Mulla S, Hall LJ, Maassen C, Lux P, Schurgers LJ, Harrington DJ. Exclusively breastmilk-fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth. J Thromb Haemost. 2022 Dec;20(12):2773-2785. doi: 10.1111/jth.15874. Epub 2022 Oct 3.
- Clarke P, Mitchell SJ, Shearer MJ. Total and Differential Phylloquinone (Vitamin K1) Intakes of Preterm Infants from All Sources during the Neonatal Period. Nutrients. 2015 Sep 25;7(10):8308-20. doi: 10.3390/nu7105393.
- Clarke P, Embleton ND, Fewtrell M, Harrington DJ, Kelly AM, Moris N, Patto A, Ponnusamy V, Vasu V, Shearer MJ. Vitamin K: missed at peril-the case for extra supplementation to prevent deficiency in breastfed preterm infants. Arch Dis Child Fetal Neonatal Ed. 2024 Oct 18;109(6):679-680. doi: 10.1136/archdischild-2023-326737. No abstract available.
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Расстройства питания
- Младенец, Новорожденный, Болезни
- Гематологические заболевания
- Нарушения свертывания крови
- Геморрагические расстройства
- Авитаминоз
- Дефицитные заболевания
- Недоедание
- Врожденные, наследственные и неонатальные заболевания и аномалии
- Поведение
- Пищевые и метаболические заболевания
- Гемики и лимфатические заболевания
- Кормление Поведение
- Дефицит витамина К
- Нарушения питания младенцев
- Кормление грудью
- Vitamin K Deficiency Bleeding
Другие идентификационные номера исследования
- 150-12-25
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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