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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Rennes University Hospital
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01388387
First received: July 1, 2011
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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 Intervention
Hepatic Transplantation
Other: Tacrolimus pharmacokinetics

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 150
Study Start Date: January 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tacrolimus pharmacokinetics Other: Tacrolimus pharmacokinetics
tacrolimus pharmacokinetics over 12 hours

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01388387

Contacts
Contact: Eric BELLISSANT, MD, PhD +33299283715 Eric.Bellissant@univ-rennes1.fr
Contact: Marie-Clémence VERDIER, PharmD +33299289197 marieclemence.verdier@chu-rennes.fr

Locations
France
Service des Maladies du Foie - Hôpital de Pontchaillou Recruiting
Rennes, France, 35033
Contact: Marianne LATOURNERIE, MD       marianne.latournerie@chu-rennes.fr   
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
Investigators
Study Chair: Eric BELLISSANT, MD, PhD Rennes University Hospital
Study Chair: Marie-Clémence VERDIER, PharmD Rennes University Hospital
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01388387     History of Changes
Other Study ID Numbers: 2010-022488-36, CIC0203/129
Study First Received: July 1, 2011
Last Updated: August 11, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Rennes University Hospital:
pharmacogenetics
pharmacokinetics
tacrolimus
genetic polymorphism
CYP3A5
liver transplantation

Additional relevant MeSH terms:
Tacrolimus
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014