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

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

Prospective and monocentric pharmacokinetic study

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Kidney Transplantation

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 Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Rennes university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hepatic and / or renal transplantation

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between drug transporters expression (RNA and protein) in PBMC and tacrolimus intra-PBMC concentration	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	During the consultation (between 2 and 24 months after the transplant)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between drug transporters RNA expression in PBMC and drug transporters protein expression in PBMC	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	During the consultation (between 2 and 24 months after the transplant)
Correlation between tacrolimus blood to intracellular ratio and adverse events.	Tacrolimus-related adverse effects as recorded on the medical record of the patient.	During the consultation (between 2 and 24 months after the transplant)
Correlation between tacrolimus intra-PBMC concentration and treatment outcome	Treatment outcome as recorded on the medical record of the patient.	During the consultation (between 2 and 24 months after the transplant)
Correlation between tacrolimus intra-PBMC concentration and comedications	Co-medications as recorded on the medical record of the patient.	During the consultation (between 2 and 24 months after the transplant)
Correlation between tacrolimus intra-PBMC concentrations and Donor Graft cell-free DNA (cf-DNA) concentration	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	During the consultation (between 2 and 24 months after the transplant)

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Florian LEMAITRE, Rennes university hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): December 16, 2020
• Study Completion (Actual): December 16, 2020

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 9, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 35RC19_30018_TRANS-TAC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No