UmbrelLACT Study: Clinical Lactation Study on the Exposure to Medicines Via Human Milk

Официальное название

Clinical Lactation Study on the Exposure to Medicines Via Human Milk: an Umbrella Study Protocol

Обзор

The goal of this observational study is to determine the concentration of medicines in human milk during maternal medicine intake. The main questions it aims to answer are: * What is the concentration of maternal medicines in human milk? * What is the (estimated) intake and exposure in the breastfed infant? Participants will be asked to * fill out a questionnaire regarding medical data of the mother and child * track medication intake for 3 days * collect milk samples during 24 hours * optionally, donate 2 blood samples of the mother and give consent to one blood sample of the child * fill out a questionnaire regarding the general health of the child.

Подробное описание

There is an immense information gap regarding safety of medicines during lactation which can result in a lack of breastfeeding adherence. According to literature, 50% of women need pharmacotherapy in the postpartum period. However, the proportion of nursing women in need of medication rises, due to later age pregnancies and the increased prevalence of chronic diseases. Evidence-based decisions on the use and selection of medicine during breastfeeding are challenging for many medicines, due to the lack of available information, such as cardiovascular compounds (e.g. atorvastatin, simvastatin), antidepressants (e.g. venlafaxine), anti-epileptics (e.g. topiramate, pregabalin), etc. This often results in unnecessary cessation of breastfeeding or poor adherence to/avoidance of pharmacological treatment.

The objective of this prospective trial is to collect information about the human milk transfer of maternal medicines, subsequent infant exposure, and general health outcome of the infant. Furthermore, the data of this clinical lactation study will be used to verify the performance of pharmacologically-based pharmacokinetic (PBPK) models to predict disposition of medicines in human milk and subsequent neonatal exposure during lactation. An umbrella protocol approach is used. This means that each request or compound for which milk samples might be collected / offered by women, will be reviewed and evaluated for feasibility and relevance.

The investigators expect to enroll 5, at maximum 15, mothers per year, who have been prescribed maternal medication for medical reasons and are breastfeeding their infant (/expressing milk) while taking this medication. The participating mother will be asked to collect milk samples and optionally to donate 2 blood samples during 24h: one at the time of milk pumping the first time after medication intake and one at the last pumping session of the 24h period. The parents can optionally consent for collecting a blood sample of the infant for the study (1-5% of the total blood volume, according to the FDA guidelines). In addition, clinical maternal and infant variables will be collected, as well as medication regimen, sampling details and general infant health information using 2 questionnaires.

To conclude, with this study data about the concentration of maternal medication in human milk, and the exposure in the nursing infant will be generated. This information is an essential first step towards evidence-based risk assessment on the use of drugs during lactation.

Вмешательства

• Другое Human milk collection
  Every time the mother would normally feed the child, we ask to collect the total milk volume for the feed from both breasts by an electric pump. For each collection, the volume and time will be noted, the container will be inverted and 5 to 10ml of that volume will be transferred in a polypropylene test tube or other tube type depending on the type of compounds (=sample to determine drug concentration in milk) for analysis (max 10% of the collected volume of each feed). The participant decides h
• Другое Optionally: maternal blood sample
  Blood collection to determine the drug concentration in plasma (6 to 10mL EDTA or other tube type, depending on the type of compound) will be performed at least within 1 hour interval with the first feeding (pumping) after medication intake, and 24 hours after medication intake (with preferable milk collection within 1 hour of blood sampling). The sample label, date and time of sampling will be noted.
• Другое Optionally: child blood sample
  Blood collection of the infant to determine systemic exposure of child(1-5% of the total blood volume, according to the FDA guidelines, in an EDTA or other tube type, depending on the type of compound,) will be performed at the same day as the maternal sampling, if parental consent is obtained. The sample label, date and time of sampling will be noted.

Первичные конечные точки

• The concentration of maternal medicines in human milk [Срок оценки: 24 hours (sampling day)]

Вторичные конечные точки (12)

• The estimated intake of medicines in the nursing infant via human milk: DID [Срок оценки: 24 hours (sampling day)]
• The estimated intake of medicines in the nursing infant via human milk: eDID - maxDID [Срок оценки: 24 hours (sampling day)]
• The estimated intake of medicines in the nursing infant via human milk: RID [Срок оценки: 24 hours (sampling day)]
• The estimated intake of medicines in the nursing infant via human milk: RIDtherapeutic [Срок оценки: 24 hours (sampling day)]
• The estimated intake of medicines in the nursing infant via human milk: Css, ave [Срок оценки: 24 hours (sampling day)]
• The systemic exposure to medicines in the nursing infant via breastfeeding: infant systemic medicine concentration [Срок оценки: 24 hours (sampling day)]
• The systemic exposure to medicines in the nursing infant via breastfeeding: infant/maternal plasma ratio [Срок оценки: 24 hours (sampling day)]
• The systemic exposure to medicines in the nursing infant via breastfeeding [Срок оценки: 24 hours (sampling day)]
• The general health status (including possible adverse effects) of the nursing infant [Срок оценки: 2 weeks (in case of an acute maternal treatment/condition) or 2 months (in case of an chronic maternal treatment/condition)]
• Evaluation of physiologically-based pharmacokinetic (PBPK) models: Concentration-time profile [Срок оценки: 24 hours]
• Evaluation of physiologically-based pharmacokinetic (PBPK) models: M/P ratio [Срок оценки: 24 hours]
• Evaluation of physiologically-based pharmacokinetic (PBPK) models: Cmax [Срок оценки: 24 hours]

Критерии участия

Критерии включения

• For breastfeeding women

• Maternal age: ≥ 18 year
• Currently exclusively or partially breastfeeding (/expressing milk) at the time of milk sampling
• Using medicines for any indication, with at least 5 half-lives of the medicine taken
• Willing to express and collect human milk
• Signed informed consent to participate and for processing their personal data
• For infants

• Gestational age at birth: ≥24 weeks
• Parental signed informed consent to participate and for processing their personal data

Критерии исключения

• Maternal age <18 years
• Mother of twins
• Not meeting the inclusion criteria

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Бельгия · 1 центр

• Universitaire Ziekenhuizen KU Leuven — Leuven

Публикации

• Del Ciampo LA, Del Ciampo IRL. Breastfeeding and the Benefits of Lactation for Women's Health. Rev Bras Ginecol Obstet. 2018 Jun;40(6):354-359. doi: 10.1055/s-0038-1657766. Epub 2018 Jul 6. PMID 29980160
• Saha MR, Ryan K, Amir LH. Postpartum women's use of medicines and breastfeeding practices: a systematic review. Int Breastfeed J. 2015 Oct 28;10:28. doi: 10.1186/s13006-015-0053-6. eCollection 2015. PMID 26516340
• Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z. PMID 29411152
• Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016 Jul;100(1):42-52. doi: 10.1002/cpt.377. Epub 2016 May 13. PMID 27060684
• Koshimichi H, Ito K, Hisaka A, Honma M, Suzuki H. Analysis and prediction of drug transfer into human milk taking into consideration secretion and reuptake clearances across the mammary epithelia. Drug Metab Dispos. 2011 Dec;39(12):2370-80. doi: 10.1124/dmd.111.040972. Epub 2011 Sep 22. PMID 21940904
• Kimura S, Morimoto K, Okamoto H, Ueda H, Kobayashi D, Kobayashi J, Morimoto Y. Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk. Arch Pharm Res. 2006 May;29(5):424-9. doi: 10.1007/BF02968594. PMID 16756089
• McNamara PJ, Burgio D, Yoo SD. Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk. J Pharmacol Exp Ther. 1992 Jun;261(3):918-23. PMID 1602396
• Nauwelaerts N, Deferm N, Smits A, Bernardini C, Lammens B, Gandia P, Panchaud A, Nordeng H, Bacci ML, Forni M, Ventrella D, Van Calsteren K, DeLise A, Huys I, Bouisset-Leonard M, Allegaert K, Annaert P. A comprehensive review on non-clinical methods to study transfer of medication into breast milk - A contribution from the ConcePTION project. Biomed Pharmacother. 2021 Apr;136:111038. doi: 10.1016/ PMID 33526310

Идентификаторы

NCT: NCT06042803 · S67204

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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