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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03425071
• Other study ID #: CAAE 41558915900000068
• Status: Recruiting
• Phase: N/A
• First received: January 30, 2018
• Last updated: February 6, 2018
• Start date: March 8, 2016
• Est. completion date: December 2018

Study information

• Verified date: January 2018
• Source: University of Sao Paulo General Hospital
• Contact: Fabiana Agena, PhD
• Phone: +551126618089
• Email: fabiana.agena[@]hc.fm.usp.br
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 2018
• Est. primary completion date: July 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation
• Rejection

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas - University of Sao Paulo	São Paulo	Sao Paulo

Sponsors (9)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	Elias David Neto, Fabiana Agena, Maria da Luz Fernandes, Nairo Massakazu Sumita, Nelson Zocoler Galante, Paschoalina Romano, Persio de Almeida Rezende Ebner, Veronica Porto Carreiro de Vasconcelos Coelho

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Romano P, Fernades ML, Ebner PAR, Oliveira ND, Okuda LM, Agena F, Mendes ME, Sumita NM, Coelho V, David-Neto E, Galante NZ. UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+ and B CD19+ lymphocytes. Journal o

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between blood and intracellular levels of tacrolimus	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.	From 1 up to 5 months post transplantation
Secondary	Correlation among intracellular levels of tacrolimus and its pharmacological effects	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.	From 1 up to 5 months post transplantation