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Breast FeedingUmbrelLACTNCT06042803

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

An observational study of Breast Feeding and Human Milk, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women onlyHealthy volunteers can take part
Conditions the study is for
Breast Feeding, Human Milk
What is being tested?
Human milk collection, Optionally: maternal blood sample and Optionally: child blood sample
How many people
30 participants
Where
1 siteBelgium
Study dates
1 Feb 2023to Feb 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

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.

Who may be able to join

  • 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
Show all 9Show fewer
  • For infants
  • Gestational age at birth: ≥24 weeks
  • Parental signed informed consent to participate and for processing their personal data

Who cannot join

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Anne Smits, MD, PhD contact

+3216343565

anne.smits@uzleuven.be

Martje Van Neste, MD contact

+32 16 32 82 06

martje.vanneste@kuleuven.be

Belgium1 site, 1 recruiting

  • Universitaire Ziekenhuizen KU Leuven

    Leuven, Vlaams-Brabant, 3000

    Anne Smits, MD, PhD, +3216343565, anne.smits@uzleuven.be

    Martje Van Neste, MD, +32 16 32 82 06, martje.vanneste@kuleuven.be

    Recruiting

Other trials in Belgium

About this study

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

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.
Read the 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.

Being tested
Human milk collection, Optionally: maternal blood sample, Optionally: child blood sample
Keywords
Infant exposure, Physiologically-based pharmacokinetic models, Neonatology, breastfeeding, Pharmacology, Medicines, Drug transfer, Medication intake
Medical subject headings
Breast Feeding

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Human milk collectionOther

    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 how the remainder of the collected milk is used. The milk samples will immediately be stored in the refrigerator (4°C) after being labeled. The samples will be collected by one of the investigators within 24 hours, will be transported on ice and frozen at -80°C until analysis.

  • Optionally: maternal blood sampleOther

    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.

  • Optionally: child blood sampleOther

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The concentration of maternal medicines in human milk

    • Quantification of the concentration of medicines in human milk: concentration, milk-to-plasma (M/P) ratio;
    • The PK parameters of medicines and relevant metabolites in human milk: area under the milk concentration-time curve (AUC), the average concentration (AUC divided by dosing interval), peak and trough milk concentrations (if available, depending on dosing regimen and lactation regimen), and time to reach peak milk concentration.
    • The PK parameters of medicines and relevant metabolites in plasma from lactating women compared to available scientific literature results, such as AUC, peak plasma concentration, time to peak plasma concentration, plasma clearance or apparent oral clearance, apparent volume of distribution and terminal half-life.

    Measured: 24 hours (sampling day)

Secondary outcomes (15)

  1. The estimated intake of medicines in the nursing infant via human milk: DID

    The daily infant dosage (DID)(mg/d)

    = ∑(total drug concentration in each milk collection x expressed milk volume in each milk collection)

    Measured: 24 hours (sampling day)

  2. The estimated intake of medicines in the nursing infant via human milk: eDID - maxDID

    The estimated Daily infant dosage (eDID)(mg/kg/d) and the infant risk (maxDID) expressed as a daily weight normalized dose (mg/kg/d), with 150mL/kg/d and 200mL/kg/d as maximum estimated milk intake, respectively. The calculation of the M/P ratio is based on the AUC on multiple time points, if possible.

    = M/P ratio x average plasma concentration x estimated milk intake

    Measured: 24 hours (sampling day)

  3. The estimated intake of medicines in the nursing infant via human milk: RID

    The relative infant dose (RID)(%)

    = [eDID (mg/kg/d)/Maternal Dosage (mg/kg/d)] x 100

    Measured: 24 hours (sampling day)

  4. The estimated intake of medicines in the nursing infant via human milk: RIDtherapeutic

    The relative infant therapeutic dose (RIDtherapeutic)(%)

    = [estimated daily infant dosage (mg/kg/d)/Daily therapeutic infant dosage (mg/kg/d)] x 100

    Measured: 24 hours (sampling day)

  5. The estimated intake of medicines in the nursing infant via human milk: Css, ave

    The average infant medicine concentration at steady state (Css, ave)(ng/mL), if oral bioavailability (F) and drug clearance (CL) are known for the paediatric population

    = oral bioavailability (F) x [eDID (mg/kg/d)/Clearance (CL; L/d)]x1000

    Measured: 24 hours (sampling day)

  6. The systemic exposure to medicines in the nursing infant via breastfeeding: infant systemic medicine concentration

    The measured infant systemic medicine concentration if the parents give consent for collection of a blood sample from the infant;

    Measured: 24 hours (sampling day)

  7. The systemic exposure to medicines in the nursing infant via breastfeeding: infant/maternal plasma ratio

    The infant/maternal plasma ratio if a blood sample from the infant is available;

    Measured: 24 hours (sampling day)

  8. The systemic exposure to medicines in the nursing infant via breastfeeding

    Rate of medicine absorption in infants through human milk (e.g., infant plasma concentration/milk concentration) if a blood sample from the infant is available;

    Measured: 24 hours (sampling day)

  9. The general health status (including possible adverse effects) of the nursing infant

    The general health status of the infant, reported by maternal questionnaire.

    Measured: 2 weeks (in case of an acute maternal treatment/condition) or 2 months (in case of an chronic maternal treatment/condition)

  10. Evaluation of physiologically-based pharmacokinetic (PBPK) models: Concentration-time profile

    Evaluation of the predictive performance of PBPK models by assessing whether the observed concentration-time profiles were within the 5th-95th percentile of the population prediction of the PBPK models.

    Measured: 24 hours

  11. Evaluation of physiologically-based pharmacokinetic (PBPK) models: M/P ratio

    Evaluation of the predictive performance of PBPK models by assessing whether the observed Milk-to-plasma ratio were within the 5th-95th percentile of the population prediction of the PBPK models.

    Measured: 24 hours

  12. Evaluation of physiologically-based pharmacokinetic (PBPK) models: Cmax

    Evaluation of the predictive performance of PBPK models by assessing whether the observed maximum concentration (Cmax) were within the 5th-95th percentile of the population prediction of the PBPK models.

    Measured: 24 hours

  13. Evaluation of physiologically-based pharmacokinetic (PBPK) models: AUC

    Evaluation of the predictive performance of PBPK models by assessing whether the observed Area-under-the-curve (AUC) were within the 5th-95th percentile of the population prediction of the PBPK models.

    Measured: 24 hours

  14. Evaluation of physiologically-based pharmacokinetic (PBPK) models: DID

    Evaluation of the predictive performance of PBPK models by comparing the predicted daily infant dosage (DID) with the calculated DID [The daily infant dosage (DID)(mg/d) = ∑(total drug concentration in each milk collection x expressed milk volume in each milk collection), calculated from the concentrations found in the human milk samples].

    Measured: 24 hours

  15. Evaluation of physiologically-based pharmacokinetic (PBPK) models: RID

    Evaluation of the predictive performance of PBPK models by comparing the predicted relative infant dose (RID) with the calculated RID [The relative infant dose (RID)(%) = [eDID (mg/kg/d)/Maternal Dosage (mg/kg/d)] x 100].

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2023
  2. Study start1 Feb 2023
  3. Primary completionDec 2026 (estimated)
  4. Study completionFeb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06042803
Sponsor's protocol ID
S67204
Acronym
UmbrelLACT
Status last verified
Jun 2024
First submitted
7 Aug 2023
Last updated
27 Feb 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 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.

    PubMed 26516340

  • Anderson PO. Drugs in Lactation. Pharm Res. 2018 Feb 6;35(3):45. doi: 10.1007/s11095-017-2287-z.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 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.

    PubMed 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/j.biopha.2020.111038. Epub 2021 Jan 30.

    PubMed 33526310

  • Garessus EDG, Mielke H, Gundert-Remy U. Exposure of Infants to Isoniazid via Breast Milk After Maternal Drug Intake of Recommended Doses Is Clinically Insignificant Irrespective of Metaboliser Status. A Physiologically-Based Pharmacokinetic (PBPK) Modelling Approach to Estimate Drug Exposure of Infants via Breast-Feeding. Front Pharmacol. 2019 Jan 22;10:5. doi: 10.3389/fphar.2019.00005. eCollection 2019.

    PubMed 30723406

  • Anderson PO, Momper JD. Clinical lactation studies and the role of pharmacokinetic modeling and simulation in predicting drug exposures in breastfed infants. J Pharmacokinet Pharmacodyn. 2020 Aug;47(4):295-304. doi: 10.1007/s10928-020-09676-2. Epub 2020 Feb 7.

    PubMed 32034606

  • Maharaj AR, Edginton AN. Physiologically based pharmacokinetic modeling and simulation in pediatric drug development. CPT Pharmacometrics Syst Pharmacol. 2014 Oct 22;3(11):e150. doi: 10.1038/psp.2014.45.

    PubMed 25353188

  • Byrne JJ, Spong CY. "Is It Safe?" - The Many Unanswered Questions about Medications and Breast-Feeding. N Engl J Med. 2019 Apr 4;380(14):1296-1297. doi: 10.1056/NEJMp1817420. No abstract available.

    PubMed 30943334

  • Nauwelaerts N, Ceulemans M, Deferm N, Eerdekens A, Lammens B, Armoudjian Y, Van Calsteren K, Allegaert K, de Vries L, Annaert P, Smits A. Case Report: Bosentan and Sildenafil Exposure in Human Milk - A Contribution From the ConcePTION Project. Front Pharmacol. 2022 Jun 15;13:881084. doi: 10.3389/fphar.2022.881084. eCollection 2022.

    PubMed 35784689

  • Jones HM, Mayawala K, Poulin P. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches. AAPS J. 2013 Apr;15(2):377-87. doi: 10.1208/s12248-012-9446-2. Epub 2012 Dec 27.

    PubMed 23269526

  • Mould DR, Upton RN. Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods. CPT Pharmacometrics Syst Pharmacol. 2013 Apr 17;2(4):e38. doi: 10.1038/psp.2013.14. No abstract available.

    PubMed 23887688

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Feeding and Human Milk, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anne Smits, MD, PhD (+3216343565, anne.smits@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The concentration of maternal medicines in human milk (time frame: 24 hours (sampling day)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06042803, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2025.

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