Cells of Monocytic Origin as Surrogate Markers for Individual Drug Effects and Hepatotoxicity
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 300
- 试验地点
- 5
- 主要终点
- Reflection of individual drug hepatotoxicity in monocyte derived cells
研究概览
简要总结
Drug metabolism in the liver is subject to large fluctuations (differences between women and men, people of different ethnic backgrounds, children and adults). These large differences are responsible for very different drug effects and side-effects (and especially liver damage caused by drugs) between individuals. Recent scientific findings suggest that blood derived cells can be used to model individual effects of drugs on the liver reflect inter-individual differences. Since liver damage caused by drugs is a diagnosis of exclusion, the aforementioned cells can be used to identify patients that show higher sensitivity to hepatotoxic side-effects and - in case several drugs are involved - identify the causal agent or possible interactions.
详细描述
Drug-induced liver injury (DILI), especially its idiosyncratic for is often an unpredictable complication of drug therapy. Until now it is very challenging to predict occurrence, severity and outcome of DILI. Previous data provide evidence that cells from peripheral blood may reflect hepatocellular damage (Fannin RD, Hepatology. 2010). Own research could show that peripheral monocytes are capable to obtain several hepatocyte-like functions while maintaining individual characteristics of the donor, especially cytochrome P450 metabolism (Benesic, Gerbes, et al, Lab Invest 2012). This study investigates the effects of potentially hepatotoxic drugs on cells generated from patient blood in comparison to the clinical presentation. Its aim is the evaluation of in vitro tests using monocyte derived cells for diagnosis and exclusion of DILI and the potential to use the patient derived-cells for mechanistic investigations of DILI. 4 groups are investigated: 1) donors without liver disease 2) patients who will start a therapy with DILI-potential; 3) DILI patients; 4) patients with liver injuries other than DILI.
Patient history and clinical data are obtained and a single blood sample will be collected after informed consent.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 2 years
- •Informed consent given by the patient or in case of inability to give informed consent informed consent of the legally nominated consultee
排除标准
- •Anemia requiring blood transfusion
- •acute or chronic hepatitis B, C or human immunodeficiency virus infection
- •lack of informed consent
结局指标
主要结局
Reflection of individual drug hepatotoxicity in monocyte derived cells
时间窗: 12 months
After blood sampling, monocyte derived cells will be generated and tested in vitro for the respective compounds in short term and up to 4 weeks. If possible, the patient will have a clinical follow up during routine care to assess liver injury , course and outcome of the disease when applicable.
次要结局
未报告次要终点
研究者
Andreas Benesic, MD
Dr. med.
Ludwig-Maximilians - University of Munich