Clinical trial NCT06042803: UmbrelLACT Study: Clinical Lactation Study on the Exposure to Medicines Via Human Milk
Official title: Clinical Lactation Study on the Exposure to Medicines Via Human Milk: an Umbrella Study Protocol
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Feeding
Human Milk
Keywords: Infant exposure
Physiologically-based pharmacokinetic models
Neonatology
breastfeeding
Pharmacology
Medicines
Drug transfer
Medication intake
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Innovative Medicines Initiative
name: BELpREG
First posted: 2023-09-21
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Clinicians from University Hospitals Leuven and other healthcare facilities can give women who are breastfeeding or expressing milk and are actively taking maternal medicines, the contact information of the study team. Furthermore, the study background and contact information of the study team are available through the BELgPREG project (www.belpreg.be), a research initiative on the use of medicines during pregnancy. The study team will not interfere with the decision to prescribe medicines or to breastfeed. If interested, women can contact a study team member who will plan an information moment (by phone or video call) to explain the study and informed consent.

Healthy volunteers are healthy breastfeeding women, \>18 years and willing to donate a milk sample and optionally a plasma sample.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: The concentration of maternal medicines in human milk
timeFrame: 24 hours (sampling day)
Secondary outcomes:
measure: The estimated intake of medicines in the nursing infant via human milk: DID
timeFrame: 24 hours (sampling day)
measure: The estimated intake of medicines in the nursing infant via human milk: eDID - maxDID
timeFrame: 24 hours (sampling day)
measure: The estimated intake of medicines in the nursing infant via human milk: RID
timeFrame: 24 hours (sampling day)
measure: The estimated intake of medicines in the nursing infant via human milk: RIDtherapeutic
timeFrame: 24 hours (sampling day)
measure: The estimated intake of medicines in the nursing infant via human milk: Css, ave
timeFrame: 24 hours (sampling day)
measure: The systemic exposure to medicines in the nursing infant via breastfeeding: infant systemic medicine concentration
timeFrame: 24 hours (sampling day)
measure: The systemic exposure to medicines in the nursing infant via breastfeeding: infant/maternal plasma ratio
timeFrame: 24 hours (sampling day)
measure: The systemic exposure to medicines in the nursing infant via breastfeeding
timeFrame: 24 hours (sampling day)
measure: The general health status (including possible adverse effects) of the nursing infant
timeFrame: 2 weeks (in case of an acute maternal treatment/condition) or 2 months (in case of an chronic maternal treatment/condition)
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: Concentration-time profile
timeFrame: 24 hours
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: M/P ratio
timeFrame: 24 hours
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: Cmax
timeFrame: 24 hours
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: AUC
timeFrame: 24 hours
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: DID
timeFrame: 24 hours
measure: Evaluation of physiologically-based pharmacokinetic (PBPK) models: RID
timeFrame: 24 hours
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen KU Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Anne Smits, MD PhD
role: PRINCIPAL_INVESTIGATOR
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