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

NCT06042803 | Recruiting

• 1 other identifier: S67204
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Feeding; Human Milk

Keywords

Infant exposure; Physiologically-based pharmacokinetic models; Neonatology; breastfeeding; Pharmacology; Medicines; Drug transfer; Medication intake

Outcome Measures

Primary Outcomes (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.

  24 hours (sampling day)

Secondary Outcomes (15)

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

  24 hours (sampling day)

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

  24 hours (sampling day)

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

  24 hours (sampling day)

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

  24 hours (sampling day)

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

  24 hours (sampling day)

Interventions

Human milk collection OTHER

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 sample OTHER

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 sample OTHER

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Maternal age \<18 years
• Mother of twins

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Innovative Medicines Initiative: collaborator
• BELpREG: collaborator

Study Sites (1)

Universitaire Ziekenhuizen KU Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Related Publications (16)

• 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 BACKGROUND

• 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 BACKGROUND

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

  PMID: 29411152 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 33526310 BACKGROUND

• 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.

  PMID: 30723406 BACKGROUND

• 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.

  PMID: 32034606 BACKGROUND

• 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.

  PMID: 25353188 BACKGROUND

• 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.

  PMID: 30943334 BACKGROUND

• 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.

  PMID: 35784689 BACKGROUND

• 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.

  PMID: 23269526 BACKGROUND

• 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.

  PMID: 23887688 BACKGROUND

• Van Neste M, Nauwelaerts N, Ceulemans M, Van Calsteren K, Eerdekens A, Annaert P, Allegaert K, Smits A. Determining the exposure of maternal medicines through breastfeeding: the UmbrelLACT study protocol-a contribution from the ConcePTION project. BMJ Paediatr Open. 2024 Apr 10;8(1):e002385. doi: 10.1136/bmjpo-2023-002385.

  PMID: 38599799 DERIVED

Related Links

• WHO Breastfeeding
• FDA General Clinical Pharmacology Considerations for Neonatal Studies for Drugs and Biological Products Guidance for Industry JULY 2022
• FDA GUIDANCE DOCUMENT Clinical Lactation Studies: Considerations for Study Design MAY 2019
• FDA GUIDANCE DOCUMENT Physiologically Based Pharmacokinetic Analyses - Format and Content Guidance for Industry SEPTEMBER 2018
• EMA Reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation - Scientific guideline

Biospecimen

Retention: SAMPLES WITH DNA

Human milk samples Optionally, plasma samples

MeSH Terms

Conditions

Breast Feeding

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Anne Smits, MD PhD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Smits, MD, PhD

CONTACT

+3216343565; anne.smits@uzleuven.be

Martje Van Neste, MD

CONTACT

+32 16 32 82 06; martje.vanneste@kuleuven.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: September 21, 2023
• Study Start: February 1, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: February 27, 2025

Record last verified: 2024-06

Locations

BE (1)