Monitoring Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood Lymphocytes of Kidney Transplant Recipients
2018年2月6日 更新者:University of Sao Paulo General Hospital
Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients
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.
研究概览
研究类型
观察性的
注册 (预期的)
45
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习联系方式
- 姓名:Fabiana Agena, PhD
- 电话号码:+551126618089
- 邮箱:fabiana.agena@hc.fm.usp.br
学习地点
-
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Sao Paulo
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São Paulo、Sao Paulo、巴西、05403900
- 招聘中
- Hospital das Clinicas - University of Sao Paulo
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接触:
- Fabiana Agena, PhD
- 电话号码:+551126618089
- 邮箱:fabiana.agena@hc.fm.usp.br
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接触:
- Nelson Z Galante, PhD
- 电话号码:+551126618089
- 邮箱:nelson.galante@hc.fm.usp.br
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 60年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
The study will include kidney transplant recipients followed at Hospital das Clínicas da Faculdade de Medicina da USP.
描述
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
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 观测模型:仅案例
- 时间观点:横截面
队列和干预
团体/队列 |
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Healthy volunteers
Healthy volunteers - subjects without exposure to tacrolimus.
Blood samples from these subjects will be used in "in vitro" experiments.
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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.
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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.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Correlation between blood and intracellular levels of tacrolimus
大体时间:From 1 up to 5 months post transplantation
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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.
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From 1 up to 5 months post transplantation
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Correlation among intracellular levels of tacrolimus and its pharmacological effects
大体时间:From 1 up to 5 months post transplantation
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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.
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From 1 up to 5 months post transplantation
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
合作者
调查人员
- 首席研究员:Nelson Z Galante, PhD、Kidney Transplantation Service - University of Sao Paulo
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2016年3月8日
初级完成 (预期的)
2018年7月1日
研究完成 (预期的)
2018年12月1日
研究注册日期
首次提交
2018年1月30日
首先提交符合 QC 标准的
2018年2月6日
首次发布 (实际的)
2018年2月7日
研究记录更新
最后更新发布 (实际的)
2018年2月7日
上次提交的符合 QC 标准的更新
2018年2月6日
最后验证
2018年1月1日
更多信息
与本研究相关的术语
其他研究编号
- CAAE 41558915900000068
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
在美国制造并从美国出口的产品
不
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.