Clinical trial NCT06342505: Tacrolimus in CD3+ T Lymphocytes
Official title: The Intracellular Pharmacokinetics of Tacrolimus in CD3+ T Lymphocytes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunosuppression
Keywords: Pharmacokinetics
Tacrolimus
Kidney transplantation
Intracellular T lymphocyte concentration
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Recipients of a kidney transplant at the Erasmus MC who receive routine tacrolimus-based immunosuppression as part of routine clinical care.

Brief summary: The goal of this study is to measure concentrations of the drug tacrolimus in both whole blood and within T lymphocytes. It will also learn on the correlation between the concentration in T lymphocytes and the effects of the drug. The main questions are:

(i) What is the ratio between the tacrolimus concentration within T lymphocytes and in whole blood?; (ii) What is the correlation between tacrolimus concentrations and the effects of the drug?

Participants will:

* Receive standard clinical care;
* Undergo two extra venipunctures for the collection of blood.

Detailed description: Rationale: The immunosuppressive drug tacrolimus is routinely monitored after kidney transplantation by measuring the whole blood, pre-dose concentration (C0). However, the C0 has a poor correlation with clinical events, most notably the risk of acute rejection. Since tacrolimus' site of action is within immune cells, the intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) has recently been proposed to better represent the active concentration. However, several studies could not demonstrate an association between the intracellular tacrolimus concentration and acute rejection. One of the possible explanations for this surprising finding is the fact the PBMC fraction is composed of several cells including lymphocytes and monocytes. In this study, the tacrolimus concentration in CD3+ T lymphocytes will be investigated as this may be a more relevant cell population than PBMCs.

Objective: To prospectively measure the intracellular tacrolimus concentration in CD3+ T lymphocytes in kidney transplant recipients. The area under the concentration-vs-time curve (AUC) of the intracellular tacrolimus concentration will be determined and used for the development of a population pharmacokinetic model. The pharmacokinetics of intra-CD3+ tacrolimus will be compared with the whole-blood concentration and will be related to important clinical events.

Study design: Observational study with additional blood sampling. Study population: Twenty-five de novo kidney transplant recipients receiving once-daily tacrolimus- as maintenance immunosuppression.

Intervention: Two extra venipunctures for the collection of blood.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Receive a kidney transplant at Erasmus MC.
* Use once-daily tacrolimus as part of routine maintenance immunosuppression starting the day of surgery.
* Written informed consent.

Exclusion Criteria:

* Receive lymphocyte depleting agents (thymoglobulin, anti-thymocyte globulin, and alemtuzumab) as an induction therapy or anti-rejection treatment before the enrolment (lymphocyte depleting agents will lower the amount of CD3+ T lymphocytes to the level that they cannot be isolated for the measurement of intracellular tacrolimus concentration).

Primary outcomes:
measure: The intracellular tacrolimus concentration in CD3+ T lymphocytes
timeFrame: Follow-up to one month post-transplantation
Secondary outcomes:
measure: Intracellular cytokine production
timeFrame: Follow-up to one month post-transplantation
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Erasmus MC
Study officials:
affiliation: Erasmus Medical Center
name: Brenda C.M. de Winter, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: