Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma

Phase 2

Completed

• Conditions: Cisplatin Adverse Reaction; Upper GI Cancer
• Interventions: Drug: Silymarin; Drug: Placebo; Drug: chemotherapy

• Registration Number: NCT01829178
• Lead Sponsor: Tehran University of Medical Sciences

Brief Summary

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.

Detailed Description

This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.

Study Timeline

• Study First Submitted: 2013-01-11
• Study First Submitted QC: 2013-04-08
• Study First Posted: 2013-04-11
• Study Start: 2013-08
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-11
• Last Update Posted: 2015-05-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control arm	chemotherapy	Placebo 420 mg daily in three divided doses for 65 days as control along with \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2\]
Exprimental: Silymarin and chemotherapy	Silymarin	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
Control arm	Placebo	Placebo 420 mg daily in three divided doses for 65 days as control along with \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2\]
Exprimental: Silymarin and chemotherapy	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

Primary Outcome Measures

Name	Time	Method
Urine concentration of NGAL	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.

Secondary Outcome Measures

Name	Time	Method
Changes in VEGF Serum concentration	up to 9 weeks	To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured.
Tissue activity of caspase 3	up to 9 weeks	To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured.

Trial Locations

Locations (1)

Tehran University of Medical Science; 🇮🇷 Tehran, Iran, Islamic Republic of