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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01388387
Recruitment Status : Recruiting
First Posted : July 6, 2011
Last Update Posted : April 20, 2017
Information provided by (Responsible Party):
Rennes University Hospital

Brief 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.

Condition or disease Intervention/treatment Phase
Hepatic Transplantation Other: Tacrolimus pharmacokinetics Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Donor and Recipient CYP3A5 Genetic Polymorphism on Tacrolimus Exposure in Patients With Hepatic Transplant
Study Start Date : January 2012
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Tacrolimus pharmacokinetics Other: Tacrolimus pharmacokinetics
tacrolimus pharmacokinetics over 12 hours

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01388387

Contact: Eric BELLISSANT, MD, PhD +33299283715
Contact: Marie-Clémence VERDIER, PharmD +33299289197

Service des Maladies du Foie - Hôpital de Pontchaillou Recruiting
Rennes, France, 35033
Contact: Marianne LATOURNERIE, MD   
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         
Sponsors and Collaborators
Rennes University Hospital
Study Chair: Eric BELLISSANT, MD, PhD Rennes University Hospital
Study Chair: Marie-Clémence VERDIER, PharmD Rennes University Hospital

Responsible Party: Rennes University Hospital Identifier: NCT01388387     History of Changes
Other Study ID Numbers: 2010-022488-36
CIC0203/129 ( Other Identifier: Center for Clinical Research of Rennes University Hospital )
First Posted: July 6, 2011    Key Record Dates
Last Update Posted: April 20, 2017
Last Verified: September 2016

Keywords provided by Rennes University Hospital:
genetic polymorphism
liver transplantation

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action