Clinical trial NCT01829178: Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma
Official title: Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Upper GI Cancer
Cisplatin Adverse Reaction
Keywords: cisplatin
nephrotoxicity
antioxidant
urine neutrophil gelatinase-associated lipocalin (NGAL)
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2013-04-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Urine concentration of NGAL
timeFrame: up to 9 weeks
Secondary outcomes:
measure: Changes in VEGF Serum concentration
timeFrame: up to 9 weeks
measure: Tissue activity of caspase 3
timeFrame: up to 9 weeks
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Science
Study officials:
affiliation: Tehran University of Medical Sciences
name: Simin Dashti-Khavidaki, Dr
role: STUDY_CHAIR
References: