Clincosm LogoSign in Get a demo

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

Sponsor
Rennes University Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT03910868
Collaborator
(none)
60
Enrollment
1
Location
5
Actual Duration (Months)
11.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Prospective and monocentric pharmacokinetic study

Condition or Disease Intervention/Treatment Phase

    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 Design

    Study Type:
    Observational
    Actual Enrollment :
    60 participants
    Observational Model:
    Case-Only
    Time Perspective:
    Prospective
    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
    Actual Study Start Date :
    Jul 16, 2020
    Actual Primary Completion Date :
    Dec 16, 2020
    Actual Study Completion Date :
    Dec 16, 2020

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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.

    3. 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.

    4. 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.

    5. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rennes University Hospital Rennes France 35033

    Sponsors and Collaborators

    • Rennes University Hospital

    Investigators

    • Principal Investigator: Florian LEMAITRE, Rennes University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Rennes University Hospital
    ClinicalTrials.gov Identifier:
    NCT03910868
    Other Study ID Numbers:
    • 35RC19_30018_TRANS-TAC
    First Posted:
    Apr 10, 2019
    Last Update Posted:
    Jan 13, 2021
    Last Verified:
    Jan 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No

    Study Results

    No Results Posted as of Jan 13, 2021