- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04400084
Using Cotyledon Perfusion to Study Drugs Transfer Across the Placenta (DRUGS-PTP)
October 24, 2022 updated by: Assistance Publique - Hôpitaux de Paris
Ex Vivo Study of Drugs Transfer Across the Placenta
Drug prescriptions are usual during pregnancy however women and their fetuses still remain an orphan population with regard to drugs efficacy and safety clinical studies.
Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies.
The aim of the study is to study the drug transfer using human placenta after delivery.
Study Overview
Detailed Description
For ethical reasons, pregnant woman are not included in clinical trials so that data regarding safety and efficacy of many drugs are scarce.
It is known that xenobiotics across the placental barrier but studies regarding quantity and mechanisms of this transfer remain insuffisant.
Among the different methodologies to evaluate drug transfer, perfusion of human cotyledon is one of the most relevant ones.
The two sides of the cotyledon, fetal and maternal ones, are perfused within the hour after delivery with EARLE medium in a double closed circuit.
The studied drug (it can be any drug given to pregnant mothers) and antipyrine (the control molecule) are added at the beginning of the three hours perfusion realized at 37°C, with maternal flow rate of 12ml/min and fetal one of 6ml/min.
Samples are collected along the perfusion and the drugs dosage will be done in the pharmacology department of Cochin Hospital.
Tissues of the cotyledon will be also collected to study the proteins, and ARNs expressed.
The drug concentrations will be analyzed by calculating fetal to maternal concentrations ratios and a fetal transfer rate (fetal drug quantity on total drug quantity at the end of the perfusion).
Then modelling on Monolix software will be done to estimate the transfer constants across the two compartments.
Modelling will allow to estimate the interindividual variability and to test covariables like sex, gestation duration, genetics, or protein expression.
Proteins will be studied by an appropriated method (western blot, or proteomic analysis).
The genetics study will consist in candidate gene approach.
Polymorphisms will be chosen in genes coding for transporters or enzymes or their regulators.
Study Type
Observational
Enrollment (Anticipated)
2000
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Jean-Marc TRELUYER, Pr
- Phone Number: 00 33 1 58 41 28 85
- Email: jean-marc.treluyer@parisdescartes.fr
Study Locations
-
-
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Paris, France, 75014
- Recruiting
- CIC Port-Royal-Cochin
-
Contact:
- Camille LE RAY
- Phone Number: 00 33 1 58 41 38 17
- Email: camille.le-ray@aphp.fr
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Sampling Method
Non-Probability Sample
Study Population
Pregnant women who give birth in the Port-Royal maternity (Paris)
Description
Inclusion Criteria:
- pregnant women older than 18 years,
- patient with social security or health insurance,
- from the 24th week of amenorrhea,
- patient who has given her consent,
Exclusion Criteria:
Maternal pathologies pre-existing pregnancy :
- diabetes-like vascular disease,
- arterial hypertension,
- known prothrombotic pathology, history of venous thrombosis or pulmonary embolism,
- maternal serology HIV+, BHV+, CHV+ and syphilis,
Pregnancy and fetal pathologies :
- pre-eclampsia,
- delayed growth in utero (can affect placental circulation),
- gestational diabetes without insulin,
- fetal malformation,
- known genetic pathology,
- Patient under tutorship or curatorship, or not speaking french,
- Patient who has not given her consent
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Pregnant mothers
Pregnant mothers who have a normal pregnancy
|
Placenta perfusion in double closed circuit, during 3 hours
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fetal transfer rate
Time Frame: At 180 minutes (end of the perfusion)
|
Quantity of drug transferred into fetal compartment/ quantity of drug in the two compartments *100
|
At 180 minutes (end of the perfusion)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ratio of concentrations
Time Frame: At 180 minutes (end of the perfusion)
|
Fetal concentration / maternal concentration *100
|
At 180 minutes (end of the perfusion)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Schneider H, Panigel M, Dancis J. Transfer across the perfused human placenta of antipyrine, sodium and leucine. Am J Obstet Gynecol. 1972 Nov 15;114(6):822-8. doi: 10.1016/0002-9378(72)90909-x. No abstract available.
- Hutson JR, Garcia-Bournissen F, Davis A, Koren G. The human placental perfusion model: a systematic review and development of a model to predict in vivo transfer of therapeutic drugs. Clin Pharmacol Ther. 2011 Jul;90(1):67-76. doi: 10.1038/clpt.2011.66. Epub 2011 May 11. Erratum In: Clin Pharmacol Ther. 2011 Sep;90(3):479.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 5, 2020
Primary Completion (Anticipated)
June 1, 2030
Study Completion (Anticipated)
June 1, 2030
Study Registration Dates
First Submitted
May 19, 2020
First Submitted That Met QC Criteria
May 19, 2020
First Posted (Actual)
May 22, 2020
Study Record Updates
Last Update Posted (Actual)
October 25, 2022
Last Update Submitted That Met QC Criteria
October 24, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- APHP190817
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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