Pharmacogenetic Study of Tacrolimus in Hepatic Transplant (CYPTAC'H)
Information source: Rennes University Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatic Transplantation
Intervention: Tacrolimus pharmacokinetics (Other)
Phase: N/A
Status: Recruiting
Sponsored by: Rennes University Hospital Official(s) and/or principal investigator(s): Eric BELLISSANT, MD, PhD, Study Chair, Affiliation: Rennes University Hospital Marie-Clémence VERDIER, PharmD, Study Chair, Affiliation: Rennes University Hospital
Overall contact: Eric BELLISSANT, MD, PhD, Phone: +33299283715, Email: Eric.Bellissant@univ-rennes1.fr
Summary
The choice of an immunosuppressant after hepatic transplant is now more difficult than
before because of the increasing number of drugs available.
Pharmacokinetic, pharmacodynamic and pharmacogenetic information can help to choose the best
treatment and the best dose for each patient. The genetic polymorphism of enzymes
metabolizing treatments can affect their efficacy and safety. Concerning tacrolimus, CYP3A5
activity is a major determinant of the dose needed to reach target concentrations. This
study is aimed at evaluating the impact of both donor and recipient CYP3A5 genetic
polymorphisms on tacrolimus exposure in patients with hepatic transplant.
Clinical Details
Official title: Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered.
Secondary outcome: Pharmacokinetics after the first administration and after 7 days of treatmentClinical follow-up during the 3 months post transplantation
Detailed description:
Pharmacogenetics is a recent tool which could help to choose the best immunosuppressive
therapy in patients with hepatic transplant. Indeed, the CYP3A5 gene has many polymorphisms
and one of them, g. 6986 A>G, is the major determinant of the variability of expression of
this protein. The allele *1 (g6986A) leads to normal protein expression while the allele *3
(g. 6986G) causes lack of protein expression, and their different combinations induce a great
variability in tacrolimus concentrations. As cytochromes are present in the liver and
intestine, in hepatic transplant, tacrolimus exposure results from both recipient
(enterocytes) and donor (liver) enzymes. Recent studies demonstrated a significant role of
the genotype recipient on the dose/concentration relationship and on the dose needed to
reach target concentrations. However, these studies were insufficient to analyze more
precisely all impacts of this polymorphism because they did not include enough patients. The
purpose of the investigators study is to evaluate the impact of donor and recipient CYP3A5
genetic polymorphism on tacrolimus exposure in patients with hepatic transplant after the
first administration of tacrolimus and at 7 days post transplantation, when the dose has
been adapted to avoid too high blood levels and to limit serious adverse reactions.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Adults (>18 years) of Caucasian origin,
- with hepatic transplant,
- who are going to be treated by tacrolimus, and
- who gave free, well-informed and written consent.
Non-inclusion Criteria:
- Participation to another protocol incompatible with the study,
- HIV patients with antiretroviral treatment,
- Patients with legal guardianship or deprived of freedom.
Locations and Contacts
Eric BELLISSANT, MD, PhD, Phone: +33299283715, Email: Eric.Bellissant@univ-rennes1.fr
Service des Maladies du Foie - Hôpital de Pontchaillou, Rennes 35033, France; Recruiting Marianne LATOURNERIE, MD, Email: marianne.latournerie@chu-rennes.fr Eric BELLISSANT, MD, PhD, Principal Investigator Christophe CAMUS, MD, Sub-Investigator Marianne LATOURNERIE, MD, Sub-Investigator Edouard BARDOU-JACQUET, MD, Sub-Investigator Karim BOUDJEMA, MD, PhD, Sub-Investigator
Additional Information
Starting date: January 2012
Last updated: August 20, 2015
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