Clinical trial NCT03910868: Impact of P-gp, MRP2, ENT-1 and CNT3 on the Blood Concentration / Intra-PBMC Concentration of Tacrolimus
Official title: Study of the Impact of P-gp, MRP2, ENT-1 and CNT3 on the Blood Concentration / Intra-PBMC Concentration of Tacrolimus in Liver and Kidney Transplant Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Transplantation
Kidney Transplantation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2019-04-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hepatic and / or renal transplantation

Brief summary: Prospective and monocentric pharmacokinetic study

Detailed description: Membrane transporters supporting tacrolimus at the lymphocyte level may play a role in the variability of the relationship between tacrolimus blood concentration and intracellular concentration, or may be the main explanatory factors. Nevertheless, most of the studies carried out on the subject, have been by genetic approach, neglecting in fact the membrane expression of these transporters, which could testify more to the real effect on the transport of tacrolimus. A better understanding of the cellular transport mechanisms of tacrolimus in the T lymphocyte could thus make it possible to identify sub-populations of patients under-exposed at the intra-lymphocyte level, despite satisfactory systemic exposure.

Eligibility criteria: Inclusion Criteria:

* Adult of 18 or over;
* fully and honestly informed, and not having reported his non-opposition to the use of his samples for research;
* Affiliated to a social security scheme;
* Hepatic and / or renal transplant stable between two and twenty-four months after transplantation, treated with tacrolimus;
* Without modification of immunosuppressive treatment or treatment likely to modify their pharmacokinetics (imidazoles, macrolides ...) during the last two weeks;
* Each patient can only be included once.

Exclusion Criteria:

* Participation in another protocol whose procedures are incompatible with the realization of the study;
* Pregnant woman ;
* Major person subject to legal protection (safeguard of justice, guardianship, tutorship);
* Person deprived of liberty;
* Opposition to the use of clinical data and remnants of samples taken from care for research purposes.

Primary outcomes:
measure: Correlation between drug transporters expression (RNA and protein) in PBMC and tacrolimus intra-PBMC concentration
timeFrame: During the consultation (between 2 and 24 months after the transplant)
Secondary outcomes:
measure: Correlation between drug transporters RNA expression in PBMC and drug transporters protein expression in PBMC
timeFrame: During the consultation (between 2 and 24 months after the transplant)
measure: Correlation between tacrolimus blood to intracellular ratio and adverse events.
timeFrame: During the consultation (between 2 and 24 months after the transplant)
measure: Correlation between tacrolimus intra-PBMC concentration and treatment outcome
timeFrame: During the consultation (between 2 and 24 months after the transplant)
measure: Correlation between tacrolimus intra-PBMC concentration and comedications
timeFrame: During the consultation (between 2 and 24 months after the transplant)
measure: Correlation between tacrolimus intra-PBMC concentrations and Donor Graft cell-free DNA (cf-DNA) concentration
timeFrame: During the consultation (between 2 and 24 months after the transplant)
Other outcomes:
Locations:
city: Rennes
country: France
facility: Rennes University Hospital
Study officials:
affiliation: Rennes University Hospital
name: Florian LEMAITRE
role: PRINCIPAL_INVESTIGATOR
References: