Pharmacogenetic Study of Tacrolimus in Hepatic Transplant (CYPTAC'H)

Hepatic Transplantation Clinical Trial

Official title:

Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01388387
• Other study ID #: 2010-022488-36
• Secondary ID: CIC0203/129
• Status: Completed
• Phase: N/A
• Start date: February 22, 2012
• Est. completion date: July 31, 2018

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: July 31, 2018
• Est. primary completion date: July 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Transplantation

Intervention

Other:
• Tacrolimus pharmacokinetics
tacrolimus pharmacokinetics over 12 hours

Locations

Country	Name	City	State
France	Service des Maladies du Foie - Hôpital de Pontchaillou	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (1)

Tron C, Woillard JB, Houssel-Debry P, David V, Jezequel C, Rayar M, Balakirouchenane D, Blanchet B, Debord J, Petitcollin A, Roussel M, Verdier MC, Bellissant E, Lemaitre F. Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Exposure to tacrolimus after the first administration, using tacrolimus area under curve (AUC) between 0 and 12 hours, weighted by the dose administered.		12 hours
Secondary	Pharmacokinetics after the first administration and after 7 days of treatment	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.	7 days
Secondary	Clinical follow-up during the 3 months post transplantation	Prescribed tacrolimus dose, tolerance of tacrolimus (hypertension, diabetes, renal insufficiency, neurological troubles) and signs of liver rejection assessed at each follow-up visit.	3 months