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

• Conditions: Rejection; Kidney Transplantation

• Registration Number: NCT03425071
• Lead Sponsor: University of Sao Paulo General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03-08
• Status Verified: 2018-01
• Study First Submitted: 2018-01-30
• Study First Submitted QC: 2018-02-06
• Last Update Submitted: 2018-02-06
• Study First Posted: 2018-02-07
• Last Update Posted: 2018-02-07
• Primary Completion: 2018-07
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Hospital das Clínicas - University of Sao Paulo; 🇧🇷 São Paulo, Sao Paulo, Brazil