Pharmacogenetic Study of Tacrolimus in Hepatic Transplant (CYPTAC'H)
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.
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant|
- Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered. [ Time Frame: 12 hours ] [ Designated as safety issue: No ]
- Pharmacokinetics after the first administration and after 7 days of treatment [ Time Frame: 7 days ] [ Designated as safety issue: No ]Maximal concentration, time needed to reach maximal concentration, residual concentration 12 hours after drug administration, terminal elimination half-life, systemic clearance, AUC 0-12h/dose.
- Clinical follow-up during the 3 months post transplantation [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]Prescribed tacrolimus dose, tolerance of tacrolimus (hypertension, diabetes, renal insufficiency, neurological troubles) and signs of liver rejection assessed at each follow-up visit.
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||July 2015|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
|Experimental: Tacrolimus pharmacokinetics||
Other: Tacrolimus pharmacokinetics
tacrolimus pharmacokinetics over 12 hours
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01388387
|Contact: Eric BELLISSANT, MD, PhD||+33299283715||Eric.Bellissant@univ-rennes1.fr|
|Contact: Marie-Clémence VERDIER, PharmDfirstname.lastname@example.org|
|Service des Maladies du Foie - Hôpital de Pontchaillou||Recruiting|
|Rennes, France, 35033|
|Contact: Marianne LATOURNERIE, MD email@example.com|
|Principal Investigator: Eric BELLISSANT, MD, PhD|
|Sub-Investigator: Christophe CAMUS, MD|
|Sub-Investigator: Marianne LATOURNERIE, MD|
|Sub-Investigator: Edouard BARDOU-JACQUET, MD|
|Sub-Investigator: Karim BOUDJEMA, MD, PhD|
|Study Chair:||Eric BELLISSANT, MD, PhD||Rennes University Hospital|
|Study Chair:||Marie-Clémence VERDIER, PharmD||Rennes University Hospital|