Pharmacogenetics of Mycophenolic Acid in Kidney Transplant Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Drug measurement of MPA, MPA-G and acyl-MPA-G
研究概览
简要总结
The purpose of this study is to determine how genes influence the response to mycophenolate mofetil (CellCept) in children who have had a kidney transplant. The study will look at how differences in some genes effect blood levels of mycophenolate mofetil over time in children, how often side effects occur and the way that children respond to mycophenolate mofetil.
The results may lead to better dosing based on individual needs.
详细描述
This is an open label, inpatient-outpatient prospective observational study to determine whether the inter-patient variability in mycophenolic acid (MPA) pharmacokinetics and exposure, adverse events and clinical response in pediatric transplant patients (ages 2-18 years) is associated with identifiable pharmacogenetic factors. Specific aims: 1.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-individual variability in MPA pharmacokinetics and exposure (by affecting MPA metabolism). 2.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-patient differences in the incidence of adverse events (by affecting the formation of the acyl-glucuronide metabolite). Enrolled subjects will have been receiving mycophenolate mofetil as part of their clinical standard of care. It is anticipated that the clinical portion of the study will last up to 4 hours at one study visit to include one pharmacogenetic blood sample and 4 pharmacokinetic blood samples collected out to 3 hours post-dose. Safety data to be collected will include standard of care physical exam and safety laboratory tests as well as data on adverse events and clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male subjects and non-pregnant female subjects aged 2 to 18 years who are about to receive a kidney transplant and will be on post transplant MMF containing immunosuppressive therapy.
- •A signed and dated institutional review board (IRB) approved parental/guardian informed consent form and an IRB approved child assent form if applicable.
- •Subjects with stable kidney allografts who are on a stable regimen of MMF (with tacrolimus and steroids)
- •May have clinically important abnormalities on clinical and /or laboratory evaluations, only as these abnormalities relate to an underlying condition as determined by the principal investigator.
排除标准
- •Children receiving cyclosporine therapy that may interact with MPA entero-hepatic recycling.
- •Any medical condition(active or chronic) or prior surgery that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.
- •Concomitant medication that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.
结局指标
主要结局
Drug measurement of MPA, MPA-G and acyl-MPA-G
时间窗: Day 1
The following outcome measures will be performed at the study visit after the patient is on a steady state dose of mycophenolate mofetil:
时间窗: Day 1
Genomic DNA extraction using standard procedures. Patients will be genotyped for the UGT2B7, UGT1A8, UGT1A9 polymorphism.
时间窗: Day 1
次要结局
- Physical Exam(Day 1)
- Safety Laboratory tests(Day 1)
- Dietary Monitoring(Day 1)
- Concomitant medications and mycophenolate mofetil drug diary(Day 1)
- Adverse Event Reporting(Day 1)