Placental Transfer of Tenofovir

Pregnant Women Clinical Trial

— TDF-PTP  

Official title:

Study of Placental Transfer of Tenofovir and Its Factors of Variability Using the Human Placental Perfusion Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02020083
• Other study ID #: NI121204
• Status: Completed
• Start date: February 2013
• Est. completion date: June 30, 2020

Study information

• Verified date: September 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 369
• Est. completion date: June 30, 2020
• Est. primary completion date: June 4, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pregnant Women

Locations

Country	Name	City	State
France	Maternité de Port Royal	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (2)

Hirt D, Urien S, Ekouévi DK, Rey E, Arrivé E, Blanche S, Amani-Bosse C, Nerrienet E, Gray G, Kone M, Leang SK, McIntyre J, Dabis F, Tréluyer JM; ANRS 12109. Population pharmacokinetics of tenofovir in HIV-1-infected pregnant women and their neonates (ANRS 12109). Clin Pharmacol Ther. 2009 Feb;85(2):182-9. doi: 10.1038/clpt.2008.201. Epub 2008 Nov 5. — View Citation

Vinot C, Gavard L, Tréluyer JM, Manceau S, Courbon E, Scherrmann JM, Declèves X, Duro D, Peytavin G, Mandelbrot L, Giraud C. Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression. Antimicrob Agents Chemother. 2013 Mar;57(3):1415-20. doi: 10.1128/AAC.01821-12. Epub 2013 Jan 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of ABC transporters gene expression levels by quantitative RT-PCR	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.	1 hour
Secondary	Fetal transfer rate (%)of emtricitabine alone, or Tenofovir alone, or in association	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.	3 hours