Impact of P-gp, MRP2, ENT-1 and CNT3 on the Blood Concentration / Intra-PBMC Concentration of Tacrolimus

Completed

• Conditions: Kidney Transplantation; Liver Transplantation

• Registration Number: NCT03910868
• Lead Sponsor: Rennes University Hospital

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.

Study Timeline

• Study First Submitted: 2019-04-04
• Study First Submitted QC: 2019-04-09
• Study First Posted: 2019-04-10
• Study Start: 2020-07-16
• Primary Completion: 2020-12-16
• Study Completion: 2020-12-16
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-12
• Last Update Posted: 2021-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Correlation between drug transporters expression (RNA and protein) in PBMC and tacrolimus intra-PBMC concentration	During the consultation (between 2 and 24 months after the transplant)	The mRNA levels will be recorded as a cycle threshold difference between the studied gene, and the mean of two housekeeping genes (ACTB and B2M). The proteic expression of the studied transporters will be recorded as fluorescent intensity levels

Secondary Outcome Measures

Name	Time	Method
Correlation between tacrolimus blood to intracellular ratio and adverse events.	During the consultation (between 2 and 24 months after the transplant)	Tacrolimus-related adverse effects as recorded on the medical record of the patient.
Correlation between tacrolimus intra-PBMC concentration and treatment outcome	During the consultation (between 2 and 24 months after the transplant)	Treatment outcome as recorded on the medical record of the patient.
Correlation between tacrolimus intra-PBMC concentration and comedications	During the consultation (between 2 and 24 months after the transplant)	Co-medications as recorded on the medical record of the patient.
Correlation between tacrolimus intra-PBMC concentrations and Donor Graft cell-free DNA (cf-DNA) concentration	During the consultation (between 2 and 24 months after the transplant)	Donor graft cf-DNA characterized the cell death marker, released from necrotic or apoptotic cells in the transplant organ, and may therefore be useful as a marker for graft injury. When its plasma concentration increases, it evidences that a lesion process occurs in the graft
Correlation between drug transporters RNA expression in PBMC and drug transporters protein expression in PBMC	During the consultation (between 2 and 24 months after the transplant)	The mRNA levels will be recorded as a cycle threshold difference between the studied gene, and the mean of two housekeeping genes (ACTB and B2M). The proteic expression of the studied transporters will be recorded as fluorescent intensity levels

Trial Locations

Locations (1)

Rennes University Hospital; 🇫🇷 Rennes, France