Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major

NCT01752153 | Completed Phase 1 DMC

• 1 other identifier: 1929
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune Abnormalities

Keywords

Focus; immunomodulatory effect; of silymarin; on cell mediated immunity; Beta-Thalassemia; major patients.

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

Silymarin (Legalon)

EXPERIMENTAL

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)

Combined therapy (Deaferrioxamine+Silymarin (Legalon)

EXPERIMENTAL

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)

Interventions

Desferrioxamine, Legalon® (Silymarin) DRUG

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

Combined therapy (Deaferrioxamine+Silymarin (Legalon)

Silymarin (Legalon) DRUG

Silymarin (Legalon)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shiraz University of Medical Sciences: lead

Study Sites (1)

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

Shiraz, Fars, Iran

Location

MeSH Terms

Conditions

beta-Thalassemia

Interventions

Deferoxamine; Silymarin

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Zahra Amirghofran, PhD

  Shiraz University of Medical Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: December 19, 2012
• Study Start: June 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: December 19, 2012

Record last verified: 2012-11

Locations

IR (1)