Clinical trial NCT03425071: Monitoring Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood Lymphocytes of Kidney Transplant Recipients
Official title: Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplantation
Rejection
Keywords: Tacrolimus
T Lymphocytes
B lymphocytes
Monitoring, Immunologic
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
Collaborators: name: Maria da Luz Fernandes
name: Paschoalina Romano
name: Persio de Almeida Rezende Ebner
name: Nairo Massakazu Sumita
name: Veronica Porto Carreiro de Vasconcelos Coelho
name: Fabiana Agena
name: Elias David Neto
name: Nelson Zocoler Galante
First posted: 2018-02-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include kidney transplant recipients followed at Hospital das Clínicas da Faculdade de Medicina da USP.

Brief summary: Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Although TDM is widely used in clinical practice, a significant number of kidney transplant recipients have acute allograft rejection in the first year after transplantation. To improve the use of immunosuppressive drugs, new approaches of TDM have been developed. Monitoring drug concentrations at lymphocytes of peripheral blood is considering promising because it indicates the availability of the drug directly in the target sites of immunosuppression. The present study intends to establish the concentration profile of tacrolimus in the peripheral blood in parallel with the concentration profile inside T and B lymphocytes of peripheral blood of kidney transplant recipients, and correlates them with the expected pharmacological effects. The pharmacological effects of tacrolimus in calcineurin dependent and calcineurin independent (mitogen-activated protein kinase (MAPK) dependent) activation pathways will be assessed by measuring activated nuclear factor of activated T cells (NFAT) and p38, respectively, by flow cytometry. The expression of interleukin (IL) - 2 and IL-10 by T and B lymphocytes, respectively, will be also used to monitoring the pharmacodynamic effects of tacrolimus.


Eligibility criteria: Inclusion Criteria:

* Kidney transplant recipients with a well functioning graft (serum creatinine ≤ 2,0 mg/dL at inclusion)
* Must be on tacrolimus therapy
* Must be on short term follow up time (1 to 5 months) after surgery

Exclusion Criteria:

* A concomitant second solid organ transplant
* Immunosuppression not containing tacrolimus

Primary outcomes:
measure: Correlation between blood and intracellular levels of tacrolimus
timeFrame: From 1 up to 5 months post transplantation
Secondary outcomes:
measure: Correlation among intracellular levels of tacrolimus and its pharmacological effects
timeFrame: From 1 up to 5 months post transplantation
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clínicas - University of Sao Paulo
state: Sao Paulo
Study officials:
affiliation: Kidney Transplantation Service - University of Sao Paulo
name: Nelson Z Galante, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Romano P, da Luz Fernandes M, de Almeida Rezende Ebner P, Duarte de Oliveira N, Mitsue Okuda L, Agena F, Mendes ME, Massakazu Sumita N, Coelho V, David-Neto E, Zocoler Galante N. UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+ and B CD19+ lymphocytes. J Pharm Biomed Anal. 2018 Apr 15;152:306-314. doi: 10.1016/j.jpba.2018.01.002. Epub 2018 Jan 5.