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

Rennes University Hospital

Status: Completed

Conditions: Hepatic Transplantation

Treatments: Other: Tacrolimus pharmacokinetics

Study type: Interventional

Funder types: Other

Identifiers

NCT01388387

2010-022488-36

CIC0203/129 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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154 participants in 1 patient group

Tacrolimus pharmacokinetics

Experimental group

Treatment:

Other: Tacrolimus pharmacokinetics