Monitoring Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood Lymphocytes of Kidney Transplant Recipients

Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03425071

Enrollment

Registered

2018-02-07

Start date

2016-03-08

Completion date

2018-12-31

Last updated

2018-02-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Transplantation, Rejection

Keywords

Tacrolimus, T Lymphocytes, B lymphocytes, Monitoring, Immunologic

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.

Interventions

None listed

Study design

Observational model

CASE_ONLY

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Correlation between blood and intracellular levels of tacrolimus	From 1 up to 5 months post transplantation	The concentration of tacrolimus will be determined in the whole blood, in T CD4+ cell suspension and in B CD19+ cell suspension prepared from one blood sample per patient subject. The correlations among concentrations of tacrolimus in the 3 different cell matrices will be established.

Secondary

Measure	Time frame	Description
Correlation among intracellular levels of tacrolimus and its pharmacological effects	From 1 up to 5 months post transplantation	The pharmacological effects of tacrolimus will be measured as the inhibition of the nuclear translocation of NFAT transcription factor, the phosphorylation state of p38 MAP kinase and the production of interleukin 2 and 10 by flow cytometry.

Countries

Brazil

Contacts

Primary ContactFabiana Agena, PhD

fabiana.agena@hc.fm.usp.br+551126618089

Outcome results