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

Sponsors

Lead Sponsor: University of Sao Paulo General Hospital

Collaborator: Maria da Luz Fernandes
Paschoalina Romano
Persio de Almeida Rezende Ebner
Nairo Massakazu Sumita
Veronica Porto Carreiro de Vasconcelos Coelho
Fabiana Agena
Elias David Neto
Nelson Zocoler Galante

Source 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.

Overall Status Unknown status
Start Date 2016-03-08
Completion Date 2018-12-01
Primary Completion Date 2018-07-01
Study Type Observational
Primary Outcome
Measure Time Frame
Correlation between blood and intracellular levels of tacrolimus From 1 up to 5 months post transplantation
Secondary Outcome
Measure Time Frame
Correlation among intracellular levels of tacrolimus and its pharmacological effects From 1 up to 5 months post transplantation
Enrollment 45
Condition
Eligibility

Sampling Method:

Non-Probability Sample

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

60 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Nelson Z Galante, PhD Principal Investigator Kidney Transplantation Service - University of Sao Paulo
Overall Contact

Last Name: Fabiana Agena, PhD

Phone: +551126618089

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Hospital das Clínicas - University of Sao Paulo Nelson Z Galante, PhD +551126618089 [email protected]
Location Countries

Brazil

Verification Date

2018-01-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Arm Group

Label: Healthy volunteers

Description: Healthy volunteers - subjects without exposure to tacrolimus. Blood samples from these subjects will be used in "in vitro" experiments.

Label: kidney transplant (KTx) months 1-2

Description: Kidney transplant recipients recruited during the months 1 to 2 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to high blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments.

Label: KTx months 4-5

Description: Kidney transplant recipients recruited during the months 4 to 5 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to standard blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments.

Patient Data No
Study Design Info

Observational Model: Case-Only

Time Perspective: Cross-Sectional

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