Urinary Ratio of the Coproporphyrins Isomers I and III and Its Relationships With Methotrexate Elimination in Patients With a Lymphoid Malignancy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 2
- 主要终点
- MTX concentrations
研究概览
简要总结
High dose methotrexate (MTX) is responsible of severe toxicity in patients in whom elimination from plasma is delayed. Factors responsible for MTX accumulation are partly known but some patients still experience toxicity despite adequate measures being taken. Our hypothesis is that renal tubular secretion may be impaired in these patients. This study aims at evaluating the performance of the UCP ratio (urinary ratio of coproporphyrins), a putative biomarker of tubular secretion, in predicting delayed MTX elimination.
详细描述
MTX is a substrate of MRP2, a renal tubular transporter encoded by the ABCC2 gene. It has been shown that single nucleotide polymorphisms (SNPs) on the ABCC2 gene are associated with impairment of MTX elimination. Mutations on the ABCC2 gene are also responsible for the Dubin-Johnson syndrome, characterised by the absence of a functional MRP2 protein. Apart from hyperbilirubinaemia, the main biological perturbation observed in this disease is a typical increase of the urinary ratio of coproporphyrins I (I+ III) (UCP ratio). Our hypothesis is that the UCP ratio could be used as a biomarker of MRP2's activity, thus predicting MTX elimination. One hundred patients treated with high dose MTX will be recruited in this prospective study. Their UCP ratio will be measured before and after MTX administration and correlated with MTX clearance. A genetic analysis will be conducted to study the five more frequents SNPs of ABCC2 in each patient.
研究设计
- 研究类型
- Observational
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
MTX concentrations
时间窗: at the end of MTX infusion and every 24-hours until concentrations reach 0,2µM.
次要结局
- Blood cells count .(before MTX infusion and at the end of hospitalisation)
- Renal function(before MTX infusion and at the end of hospitalisation)
- The UCP I/(I+III) ratio(before and at the end of MTX infusion and at the end of hospitalisation.)
- Five polymorphisms of the ABCC2 gene (-24C/T, 1249G/A, 3563T/A, 4544G/A)(during the study)