Tacrolimus in CD3+ T Lymphocytes

Immunosuppression Clinical Trial

— INTACT  

Official title:

The Intracellular Pharmacokinetics of Tacrolimus in CD3+ T Lymphocytes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06342505
• Other study ID #: MEC-2022-0037
• Status: Completed
• Start date: May 30, 2022
• Est. completion date: November 10, 2022

Study information

• Verified date: March 2024
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: November 10, 2022
• Est. primary completion date: October 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Immunosuppression

Intervention

Procedure:
• Venipunctures
Extra venipunctures

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The intracellular tacrolimus concentration in CD3+ T lymphocytes	The tacrolimus concentration in T lymphocytes will be measured by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The concentration measured is reported in µg/L. The intracellular tacrolimus concentration will then be calculated and reported in pg/million cells (range 5-1,250 pg/million cells).	Follow-up to one month post-transplantation
Secondary	Intracellular cytokine production	=CD3+ T lymphocytes will be stimulated in vivo by CD3/CD28 magnetic beads overnight. Cytokines produced by CD3+ T lymphocytes, including IL-2 and IFN-?, will be measured by the intracellular staining under flow cytometry.	Follow-up to one month post-transplantation