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Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major

Phase 1
Completed
Conditions
Immune Abnormalities
Interventions
Drug: Silymarin (Legalon)
Drug: Desferrioxamine, Legalon® (Silymarin)
Registration Number
NCT01752153
Lead Sponsor
Shiraz University of Medical Sciences
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Silymarin (Legalon)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.
Combined therapy (Deaferrioxamine+Silymarin (Legalon)Desferrioxamine, Legalon® (Silymarin)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.
Primary Outcome Measures
NameTimeMethod
Change from Baseline in T cell proliferation12 weeks

PHA-activated T Cell Proliferation in Cell Culture was studied by Brdu Incorporation ELISA-based Assay

Changes from baseline the percentage of lymphocyte subsets12 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 cells12 weeks

The concentrations of IL-2, IL-4, and IFN-gamma in supernatant of activated T cells were measured using ELISA assay.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences

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Shiraz, Fars, Iran, Islamic Republic of

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