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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01829178
Recruitment Status : Completed
First Posted : April 11, 2013
Last Update Posted : May 13, 2015
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Upper GI Cancer Cisplatin Adverse Reaction Drug: Silymarin Drug: Placebo Drug: chemotherapy Phase 2 Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity
Study Start Date : August 2013
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: 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]
Drug: Placebo
placebo tablets: 420 mg in 3 divided dose
Other Name: Identical inert tablet to mimic silymarin (140 mg)

Drug: chemotherapy
All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2
Other Names:
  • Cisplatin
  • fluorouracil
  • Docetaxel

Active Comparator: 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
Drug: Silymarin
Silymarin 420 mg in 3 divided dose plus standard chemotherapy
Other Name: Milk thistle

Drug: chemotherapy
All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2
Other Names:
  • Cisplatin
  • fluorouracil
  • Docetaxel




Primary Outcome Measures :
  1. Urine concentration of NGAL [ Time Frame: 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 :
  1. Changes in VEGF Serum concentration [ Time Frame: up to 9 weeks ]
    To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured.

  2. Tissue activity of caspase 3 [ Time Frame: up to 9 weeks ]
    To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01829178


Locations
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Iran, Islamic Republic of
Tehran University of Medical Science
Tehran, Iran, Islamic Republic of
Sponsors and Collaborators
Tehran University of Medical Sciences
Investigators
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Study Chair: Simin Dashti-Khavidaki, Dr Tehran University of Medical Sciences
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Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT01829178    
Other Study ID Numbers: 91-03-33-18878
First Posted: April 11, 2013    Key Record Dates
Last Update Posted: May 13, 2015
Last Verified: May 2015
Keywords provided by Tehran University of Medical Sciences:
cisplatin
nephrotoxicity
antioxidant
urine neutrophil gelatinase-associated lipocalin (NGAL)
Additional relevant MeSH terms:
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Cisplatin
Docetaxel
Fluorouracil
Silymarin
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antioxidants
Protective Agents