Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major

Study Overview
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Brief Summary
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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.

Conditions
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Immune Abnormalities

Intervention / Treatment
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* Drug: Desferrioxamine, Legalon® (Silymarin)
* Drug: Silymarin (Legalon)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Silymarin (Legalon)<br>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)<br> <br> |
| Experimental: Combined therapy (Deaferrioxamine+Silymarin (Legalon)<br>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)<br>* Desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Focus, immunomodulatory effect, of silymarin, on cell mediated immunity, Beta-Thalassemia, major patients.