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Placental Transfer of Tenofovir (TDF-PTP)

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ClinicalTrials.gov Identifier: NCT02020083
Recruitment Status : Recruiting
First Posted : December 24, 2013
Last Update Posted : July 20, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The purposes of this study are to determine whether transporters expression levels and drug interaction between TDF and FTC could contribute to modulate the placental transfer of this drug or. To test this hypothesis, an ex vivo model known as "the perfused ex vivo cotyledon model" allows to reproduce the conditions of the third trimester of pregnancy

Condition or disease
Pregnant Women

Detailed Description:
Nowadays, mother-to-child HIV transmission is the main cause of paediatric HIV infections. Yet, this way of transmission is effectively limited by the use of antiretroviral therapies during pregnancy in HIV infected women. The study TEmAA (ANRS 12109) we conducted allowed us to suggest a therapeutic scheme of administration of the association tenofovir disoproxil fumarate (TDF) - emtricitabine (FTC) to reduce the risk of postpartum resistance that may occur with the administration of a single dose of nevirapine before delivery. However, we also observed a large interindividual variability of TDF in vivo placental transfer that remained unexplained. Placental membrane transporters, including efflux transporters belonging the ABC transporter superfamily and uptake transporters, may constitute a source of variability. In this case, we showed such an association for maraviroc with a significant inverse correlation between its clearance index and the placental expression level of several efflux transporters of the ABCC/MRP family. Regarding TDF, it has been shown that this drug is a substrate of several efflux transporters (ABCC2/MRP2, ABCC4/MRP4, ABCC10/MRP7) and an uptake transporter (hOAT3). As these transporters are expressed on the placental barrier, it may be hypothesized that their expression levels could contribute to modulate the placental transfer of this drug. To test this hypothesis, an ex vivo model known as "the perfused ex vivo cotyledon model" allows to reproduce the conditions of the third trimester of pregnancy. Our first aim is to evaluate the potential effect of ABCC2, ABCC4, ABCC10 and hOAT3 placental expression on TDF placental transfer (First year). We also want to investigate whether a potential interaction between TDF and FTC could take part to variability.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Study of Placental Transfer of Tenofovir and Its Factors of Variability Using the Human Placental Perfusion Model
Study Start Date : February 2013
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Tenofovir




Primary Outcome Measures :
  1. Determination of ABC transporters gene expression levels by quantitative RT-PCR [ Time Frame: 1 hour ]
    Placental villi were extracted To study the expression level of transporters that may affect the placental transfer. Gene expression was evaluated for each sample using the cycle threshold value (CT), defined as the fraction cycle number at which the fluorescence generated by SYBR green dye-amplicon complex formation passes a fixed threshold above the baseline.


Secondary Outcome Measures :
  1. Fetal transfer rate (%)of emtricitabine alone, or Tenofovir alone, or in association [ Time Frame: 3 hours ]
    Placental perfusion with Emtricitabine alone, then with Tenofovir alone, and together. Fetal transfer rate of (FTR) was calculated as follow : (Cf*Vf)*100/ ((Cf*Vf)+(Cm*Vm))where Cf denotes the fetal concentration, Vf, the volume of fetal perfusate, Cm, the maternal concentration and Vm, the volume maternal perfusate.


Biospecimen Retention:   Samples With DNA
Tissue samples will be collected. The expression levels of several efflux transporters (ABCC2/MRP2, ABCC4/MRP4, ABCC10/MRP7) and an uptake transporter (hOAT3) will be determined to explain the variability of placental transfer.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women (at term >37 to 41 weeks of gestational age) without complications during pregnancy
Criteria

Inclusion Criteria:

  • Major Patients > or = 18 years old
  • At term between 37 and 41 weeks of gestational age
  • Uncomplicated pregnancy
  • Informed Consent Form signed

Exclusion Criteria:

  • Women HIV+, HBV+ or HBC+
  • Women with cardiovascular diseases such as diabetes or preeclampsia, IUGR
  • Women who had taken medications during pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02020083


Contacts
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Contact: Laurence Lecomte, PhD +33171196494 laurence.lecomte@nck.aphp.fr

Locations
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France
Maternité de Port Royal Recruiting
Paris, France
Contact: Jean-Marc Tréluyer, MD, PhD    01 58 41 28 84    jm.treluyer@svp.aphp.fr   
Contact: laurence lecomte, PhD    +33 1 58413545    Laurence.lecomte@cch.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Jean Marc Treluyer, MD, PhD APHP
Publications:
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02020083    
Other Study ID Numbers: NI121204
First Posted: December 24, 2013    Key Record Dates
Last Update Posted: July 20, 2020
Last Verified: July 2020
Keywords provided by Assistance Publique - Hôpitaux de Paris:
VIH ; Placental transfer ; Tenofovir ; Emtricitabine ; Membrane transporter