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
1 other identifier
observational
45
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Mar 2016
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 8, 2016
CompletedFirst Submitted
Initial submission to the registry
January 30, 2018
CompletedFirst Posted
Study publicly available on registry
February 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2018
CompletedFebruary 7, 2018
January 1, 2018
2.3 years
January 30, 2018
February 6, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (1)
Correlation among intracellular levels of tacrolimus and its pharmacological effects
From 1 up to 5 months post transplantation
Study Arms (3)
Healthy volunteers
Healthy volunteers - subjects without exposure to tacrolimus. Blood samples from these subjects will be used in "in vitro" experiments.
kidney transplant (KTx) months 1-2
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.
KTx months 4-5
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.
Eligibility Criteria
The study will include kidney transplant recipients followed at Hospital das Clínicas da Faculdade de Medicina da USP.
You may qualify if:
- Must be on tacrolimus therapy
- Must be on short term follow up time (1 to 5 months) after surgery
You may not qualify if:
- A concomitant second solid organ transplant
- Immunosuppression not containing tacrolimus
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Sao Paulo General Hospitallead
- Maria da Luz Fernandescollaborator
- Paschoalina Romanocollaborator
- Persio de Almeida Rezende Ebnercollaborator
- Nairo Massakazu Sumitacollaborator
- Veronica Porto Carreiro de Vasconcelos Coelhocollaborator
- Fabiana Agenacollaborator
- Elias David Netocollaborator
- Nelson Zocoler Galantecollaborator
Study Sites (1)
Hospital das Clínicas - University of Sao Paulo
São Paulo, São Paulo, 05403900, Brazil
Related Publications (1)
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.
PMID: 29471254RESULT
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Nelson Z Galante, PhD
Kidney Transplantation Service - University of Sao Paulo
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE ONLY
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 30, 2018
First Posted
February 7, 2018
Study Start
March 8, 2016
Primary Completion
July 1, 2018
Study Completion
December 1, 2018
Last Updated
February 7, 2018
Record last verified: 2018-01
Data Sharing
- IPD Sharing
- Will not share