<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04400084</url>
  </required_header>
  <id_info>
    <org_study_id>APHP190817</org_study_id>
    <nct_id>NCT04400084</nct_id>
  </id_info>
  <brief_title>Using Cotyledon Perfusion to Study Drugs Transfer Across the Placenta</brief_title>
  <acronym>DRUGS-PTP</acronym>
  <official_title>Ex Vivo Study of Drugs Transfer Across the Placenta</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Drug prescriptions are usual during pregnancy however women and their fetuses still remain an&#xD;
      orphan population with regard to drugs efficacy and safety clinical studies. Most xenobiotics&#xD;
      diffuse through the placenta and some of them can alter fetus development resulting in&#xD;
      structural abnormalities, growth or functional deficiencies. The aim of the study is to study&#xD;
      the drug transfer using human placenta after delivery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      For ethical reasons, pregnant woman are not included in clinical trials so that data&#xD;
      regarding safety and efficacy of many drugs are scarce. It is known that xenobiotics across&#xD;
      the placental barrier but studies regarding quantity and mechanisms of this transfer remain&#xD;
      insuffisant. Among the different methodologies to evaluate drug transfer, perfusion of human&#xD;
      cotyledon is one of the most relevant ones. The two sides of the cotyledon, fetal and&#xD;
      maternal ones, are perfused within the hour after delivery with EARLE medium in a double&#xD;
      closed circuit. The studied drug (it can be any drug given to pregnant mothers) and&#xD;
      antipyrine (the control molecule) are added at the beginning of the three hours perfusion&#xD;
      realized at 37°C, with maternal flow rate of 12ml/min and fetal one of 6ml/min. Samples are&#xD;
      collected along the perfusion and the drugs dosage will be done in the pharmacology&#xD;
      department of Cochin Hospital. Tissues of the cotyledon will be also collected to study the&#xD;
      proteins, and ARNs expressed. The drug concentrations will be analyzed by calculating fetal&#xD;
      to maternal concentrations ratios and a fetal transfer rate (fetal drug quantity on total&#xD;
      drug quantity at the end of the perfusion). Then modelling on Monolix software will be done&#xD;
      to estimate the transfer constants across the two compartments. Modelling will allow to&#xD;
      estimate the interindividual variability and to test covariables like sex, gestation&#xD;
      duration, genetics, or protein expression. Proteins will be studied by an appropriated method&#xD;
      (western blot, or proteomic analysis). The genetics study will consist in candidate gene&#xD;
      approach. Polymorphisms will be chosen in genes coding for transporters or enzymes or their&#xD;
      regulators.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 5, 2020</start_date>
  <completion_date type="Anticipated">June 2030</completion_date>
  <primary_completion_date type="Anticipated">June 2030</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Fetal transfer rate</measure>
    <time_frame>At 180 minutes (end of the perfusion)</time_frame>
    <description>Quantity of drug transferred into fetal compartment/ quantity of drug in the two compartments *100</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ratio of concentrations</measure>
    <time_frame>At 180 minutes (end of the perfusion)</time_frame>
    <description>Fetal concentration / maternal concentration *100</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">2000</enrollment>
  <condition>Normal Pregnancy</condition>
  <arm_group>
    <arm_group_label>Pregnant mothers</arm_group_label>
    <description>Pregnant mothers who have a normal pregnancy</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placenta perfusion</intervention_name>
    <description>Placenta perfusion in double closed circuit, during 3 hours</description>
    <arm_group_label>Pregnant mothers</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women who give birth in the Port-Royal maternity (Paris)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pregnant women older than 18 years,&#xD;
&#xD;
          -  patient with social security or health insurance,&#xD;
&#xD;
          -  from the 24th week of amenorrhea,&#xD;
&#xD;
          -  patient who has given her consent,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Maternal pathologies pre-existing pregnancy :&#xD;
&#xD;
               -  diabetes-like vascular disease,&#xD;
&#xD;
               -  arterial hypertension,&#xD;
&#xD;
               -  known prothrombotic pathology, history of venous thrombosis or pulmonary&#xD;
                  embolism,&#xD;
&#xD;
               -  maternal serology HIV+, BHV+, CHV+ and syphilis,&#xD;
&#xD;
          -  Pregnancy and fetal pathologies :&#xD;
&#xD;
               -  pre-eclampsia,&#xD;
&#xD;
               -  delayed growth in utero (can affect placental circulation),&#xD;
&#xD;
               -  gestational diabetes without insulin,&#xD;
&#xD;
               -  fetal malformation,&#xD;
&#xD;
               -  known genetic pathology,&#xD;
&#xD;
          -  Patient under tutorship or curatorship, or not speaking french,&#xD;
&#xD;
          -  Patient who has not given her consent&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jean-Marc TRELUYER, Pr</last_name>
    <phone>00 33 1 58 41 28 85</phone>
    <email>jean-marc.treluyer@parisdescartes.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie BENHAMMANI-GODARD</last_name>
    <phone>00 33 1 54 41 12 11</phone>
    <email>marie.godard@aphp.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CIC Port-Royal-Cochin</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Camille LE RAY</last_name>
      <phone>00 33 1 58 41 38 17</phone>
      <email>camille.le-ray@aphp.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>4676572</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21562489</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 22, 2020</study_first_posted>
  <last_update_submitted>October 24, 2022</last_update_submitted>
  <last_update_submitted_qc>October 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Placenta</keyword>
  <keyword>Drug</keyword>
  <keyword>Transplacental transfer</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04400084
org study id: APHP190817
nct id: NCT04400084
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Case-Only
time perspective: Prospective
measure: Fetal transfer rate
time frame: At 180 minutes (end of the perfusion)
description: Quantity of drug transferred into fetal compartment/ quantity of drug in the two compartments *100
measure: Ratio of concentrations
time frame: At 180 minutes (end of the perfusion)
description: Fetal concentration / maternal concentration *100
arm group label: Pregnant mothers
description: Pregnant mothers who have a normal pregnancy
intervention type: Other
intervention name: Placenta perfusion
description: Placenta perfusion in double closed circuit, during 3 hours
arm group label: Pregnant mothers
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jean-Marc TRELUYER, Pr
phone: 00 33 1 58 41 28 85
email: jean-marc.treluyer@parisdescartes.fr
last name: Marie BENHAMMANI-GODARD
phone: 00 33 1 54 41 12 11
email: marie.godard@aphp.fr
facility: 
status: Recruiting
contact: 
country: France
citation: 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.
PMID: 4676572
citation: 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.
PMID: 21562489
responsible party type: Sponsor
sharing ipd: No