Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Urine concentration of NGAL
研究概览
简要总结
Cisplatin is a potent chemotherapeutic agent that has been widely used to treat many solid tumours. acute renal failure, despite conservative fluid and electrolyte management, frequently reported adverse event and limiting cisplatin use. Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, anticancer and in animal model nephroprotective properties. Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury due to cisplatin. Milk thistle extract inhibitory effects on epidermal growth factor receptor, vascular endothelial growth factor and insulin-like growth factor-I have shown in the previous in-vitro studies.The aim of present study,a randomized double-blind placebo- controlled clinical trial, to investigate the therapeutic effect of silymarin on cisplatin induced nephrotoxicity and it's impact on chemotherapy. Fifty-eight patients with diagnosed upper gastrointestinal tract carcinomas randomized to silymarin (420mg) or placebo plus chemotherapy [cisplatin 50-60 mg/m2, 5-fluorouracil mg/m2, docetaxel 60-80 mg/m2 every 21 days] for 63 day after inclusion. serum creatinin, blood urea nitrogen (BUN), serum and urine electrolyte will be measured daily during chemotherapy.
changes in urine NGAL, serum vascular endothelial growth factor (VEGF)and caspase activity assessed up to 64 days.
详细描述
This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age>18 years
- •diagnosed
- •measurable upper gastrointestinal adenocarcinoma
- •swallow problem
- •would like to participate in the study
- •Glomerular filtration rate(GFR)>45ml/min/1.73m2
排除标准
- •end stage renal disease
- •requiring dialysis
- •post transplantation
- •receiving contrast media during last 72 hours
- •chronic use of corticosteroids
- •chronic use of angiotensin-converting enzyme inhibitor(ACEI )
- •untreated hypo-and hyperthyroidism
- •ejection fraction<60%
- •active urinary tract infection
- •iver disease ( five fold increase of liver enzyme in asymptomatic or 3 fold increase in symptomatic
- •use of other nephrotoxic agents such as aminoglycoside, amphotericin
- •karnofsky performance status <70
研究组 & 干预措施
Exprimental: Silymarin and chemotherapy
silymarin 420 mg daily in three divided doses for 65 days along with standard chemotherapy [cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2 control
干预措施: Silymarin (Drug)
Control arm
Placebo 420 mg daily in three divided doses for 65 days as control along with [cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2]
干预措施: Placebo (Drug)
Control arm
Placebo 420 mg daily in three divided doses for 65 days as control along with [cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2]
干预措施: chemotherapy (Drug)
Exprimental: Silymarin and chemotherapy
silymarin 420 mg daily in three divided doses for 65 days along with standard chemotherapy [cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2 control
干预措施: chemotherapy (Drug)
结局指标
主要结局
Urine concentration of NGAL
时间窗: up to 9 weeks
All subject receive silymarin at dose of 420mg or placebo in three dose for 65 consecutive day, urine NGAL concentration will be measured.
次要结局
- Changes in VEGF Serum concentration(up to 9 weeks)
- Tissue activity of caspase 3(up to 9 weeks)