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

May 22, 2023 updated by: Rennes University Hospital

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

154

Phase

  • Not Applicable

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

  • France
      • Rennes, France, 35033
        • Service des Maladies du Foie - Hôpital de Pontchaillou

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

Description

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.

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

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tacrolimus pharmacokinetics
Other: Tacrolimus pharmacokinetics
tacrolimus pharmacokinetics over 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
12 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics after the first administration and after 7 days of treatment
Time Frame: 7 days
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
Clinical follow-up during the 3 months post transplantation
Time Frame: 3 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rennes University Hospital

Investigators

  • Study Chair: Marie-Clémence VERDIER, PharmD, Rennes University Hospital
  • Study Chair: Eric BELLISSANT, MD, PhD, Rennes University Hospital

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

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 22, 2012

Primary Completion (Actual)

July 31, 2018

Study Completion (Actual)

July 31, 2018

Study Registration Dates

First Submitted

July 1, 2011

First Submitted That Met QC Criteria

July 5, 2011

First Posted (Estimate)

July 6, 2011

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 22, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-022488-36
  • CIC0203/129 (Other Identifier: Center for Clinical Research of Rennes University Hospital)

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.

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