Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major

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.

Study Overview

• Status: Completed
• Conditions: Immune Abnormalities
• Intervention / Treatment: Drug: Silymarin (Legalon); Drug: Desferrioxamine, Legalon® (Silymarin)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Fars
    • Shiraz, Fars, Iran, Islamic Republic of
      • Department of Immunology, School of Medicine, Shiraz University of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.	Drug: Desferrioxamine, Legalon® (Silymarin); Desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy)

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): September 1, 2012

Study Registration Dates

• First Submitted: November 21, 2012
• First Submitted That Met QC Criteria: December 18, 2012
• First Posted (ESTIMATE): December 19, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 19, 2012
• Last Update Submitted That Met QC Criteria: December 18, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Beta-Thalassemia; Focus; immunomodulatory effect; of silymarin; on cell mediated immunity; major patients.
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferoxamine; Silymarin
• Other Study ID Numbers: 1929