Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major

• ClinicalTrials.gov Identifier: NCT01752153
• Recruitment Status: Completed
• First Posted: December 19, 2012
• Last Update Posted: December 19, 2012
• Sponsor: Shiraz University of Medical Sciences
• Information provided by (Responsible Party): Marjan Gharagozloo, Isfahan University of Medical Sciences

Tracking Information

• First Submitted Date: November 21, 2012
• First Posted Date: December 19, 2012
• Last Update Posted Date: December 19, 2012
• Study Start Date: June 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 18, 2012)

• Change from Baseline in T cell proliferation [ Time Frame: 12 weeks ]
  PHA-activated T Cell Proliferation in Cell Culture was studied by Brdu Incorporation ELISA-based Assay
• Changes from baseline the percentage of lymphocyte subsets [ Time Frame: 12 weeks ]
  The percentage of T cell, B cell, and NK cells were studied using flowcytometry
• Changes from baseline the production of cytokines in activated T cells [ Time Frame: 12 weeks ]
  The concentrations of IL-2, IL-4, and IFN-gamma in supernatant of activated T cells were measured using ELISA assay.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major
• Official Title: Not Provided
• Brief Summary: A wide spectrum of immune abnormalities has been described by numerous studies involving β-thalassemic patients with multiple transfusions. The abnormalities observed are both quantitative and functional, and concern several components of the immune response. Flavonoids are phenolic compounds widely distributed in plants, which were reported to exert multiple biological effects, including antioxidant and free radical scavenging abilities. Silymarin, a flavonolignan complex isolated from milk thistle (Silybum marianum L. Gaertn), have been classified as cytoprotective, antioxidant, anti-inflammatory, and especially as hepatoprotective agents. Silymarin is already being used clinically for treatment of liver diseases.It is considered safe and well-tolerated, with reported adverse events similar to placebo. Several studies have also reported immunomodulatory actions of silymarin. It increases lymphocyte proliferation, interferon gamma, interleukin (IL)-4 and IL-10 secretions by stimulated lymphocytes in a dose-dependent manner. It has been shown that in vitro treatment of peripheral blood mononuclear cells with silymarin causes restoration of the thiol status and increases in T cell proliferation and activation. Because reactive oxygen species and iron overload play important roles in the pathophysiology of thalassemia, silymarin may be an effective therapy due to its antioxidant, immunomodulatory, cytoprotective and iron chelating activities. The present study designed to investigate the therapeutic activity of orally administered silymarin for treatment of β-thalassemia major, a well-known and prevalent disease in Iran, which is associated with oxidative stress, iron overload and immune abnormalities.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Immune Abnormalities

Intervention

• Drug: Desferrioxamine, Legalon® (Silymarin)
  Desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy)
• Drug: Silymarin (Legalon)

Study Arms

• Experimental: Silymarin (Legalon)
  Patients who were unable or unwilling to use desferrioxamine or had stopped desferrioxamine treatment for at least 6 months, were received only silymarin.
  Intervention: Drug: Silymarin (Legalon)
• Experimental: Combined therapy (Deaferrioxamine+Silymarin (Legalon)
  In combined therapy group, patients continued desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy) was added to desferrioxamine regimen at the dose of 140 mg, taken orally, three times a day, 7 days a week.
  Intervention: Drug: Desferrioxamine, Legalon® (Silymarin)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 18, 2012): 25
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Homozygous beta-thalassemia major
• Regularly blood transfusion
• Iron chelation therapy with subcutaneous desferrioxamine (DFO)40.0 mg/Kg/day for 5-7 days/week

Exclusion Criteria:

• Chronic hepatitis B infection
• Active hepatitis C infection
• A history of a positive HIV test
• Chronic renal or heart failure
• Iron chelation therapy with deferiprone
• Pregnancy
• Gastrointestinal conditions preventing absorption of an oral medication o
• noncompliance with prescribed therapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Iran, Islamic Republic of

Administrative Information

• NCT Number: NCT01752153
• Other Study ID Numbers: 1929
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Marjan Gharagozloo, Isfahan University of Medical Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Shiraz University of Medical Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Zahra Amirghofran, PhD; Shiraz University of Medical Sciences

• PRS Account: Shiraz University of Medical Sciences
• Verification Date: November 2012