- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02020083
Placental Transfer of Tenofovir (TDF-PTP)
October 1, 2021 updated by: Assistance Publique - Hôpitaux de Paris
Study of Placental Transfer of Tenofovir and Its Factors of Variability Using the Human Placental Perfusion Model
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
Study Overview
Status
Completed
Conditions
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.
Study Type
Observational
Enrollment (Actual)
369
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Paris, France
- Maternité de Port Royal
-
-
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
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Sampling Method
Non-Probability Sample
Study Population
Pregnant women (at term >37 to 41 weeks of gestational age) without complications during pregnancy
Description
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
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: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1 hour
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
3 hours
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Jean Marc Treluyer, MD, PhD, APHP
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
- Hirt D, Urien S, Ekouevi DK, Rey E, Arrive E, Blanche S, Amani-Bosse C, Nerrienet E, Gray G, Kone M, Leang SK, McIntyre J, Dabis F, Treluyer 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.
- Vinot C, Gavard L, Treluyer JM, Manceau S, Courbon E, Scherrmann JM, Decleves 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.
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)
February 1, 2013
Primary Completion (Actual)
June 4, 2020
Study Completion (Actual)
June 30, 2020
Study Registration Dates
First Submitted
July 4, 2013
First Submitted That Met QC Criteria
December 18, 2013
First Posted (Estimate)
December 24, 2013
Study Record Updates
Last Update Posted (Actual)
October 4, 2021
Last Update Submitted That Met QC Criteria
October 1, 2021
Last Verified
September 1, 2021
More Information
Terms related to this study
Other Study ID Numbers
- NI121204
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.
Clinical Trials on Pregnant Women
-
Myant Medical Corp.McMaster UniversityNot yet recruiting
-
Qianfoshan HospitalShandong Nursing AssociationRecruiting
-
Brigham and Women's HospitalEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsRecruitingPregnant WomenUnited States
-
Sultan Abdulhamid Han Training and Research Hospital...RecruitingPregnant WomenTurkey
-
Sultan Abdulhamid Han Training and Research Hospital...Not yet recruiting
-
Alexandria UniversityCompleted
-
University of BeykentIstanbul University - Cerrahpasa (IUC)Completed
-
Anhui Provincial HospitalAalto UniversityCompleted
-
Centre Hospitalier Universitaire Saint PierreCompleted