Immune AbnormalitiesPhase 1NCT01752153
Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major
A Phase 1 study testing Desferrioxamine, Legalon® (Silymarin) and Silymarin (Legalon) in people with Immune Abnormalities, run by Shiraz University of Medical Sciences at 1 site in Iran.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Immune Abnormalities
- What is being tested?
- Desferrioxamine, Legalon® (Silymarin) and Silymarin (Legalon)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteIran
- Study dates
- Jun 2012to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Homozygous beta-thalassemia major
- Regularly blood transfusion
- Iron chelation therapy with subcutaneous desferrioxamine (DFO)40.0 mg/Kg/day for 5-7 days/week
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Iran1 site
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences
Shiraz, Fars
About this study
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
- Being tested
- Desferrioxamine, Legalon® (Silymarin), Silymarin (Legalon)
- Keywords
- Focus, immunomodulatory effect, of silymarin, on cell mediated immunity, Beta-Thalassemia, major patients.
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Desferrioxamine, Legalon® (Silymarin)Drug
Desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy)
Silymarin (Legalon)Drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Desferrioxamine, Legalon® (Silymarin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in T cell proliferation
PHA-activated T Cell Proliferation in Cell Culture was studied by Brdu Incorporation ELISA-based Assay
Measured: 12 weeks
Changes from baseline the percentage of lymphocyte subsets
The percentage of T cell, B cell, and NK cells were studied using flowcytometry
Measured: 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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2012 (estimated)
- Study startJun 2012
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune AbnormalitiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shiraz University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marjan Gharagozloo, Isfahan University of Medical Sciences
- Investigators
- Zahra Amirghofran, PhD, Study director, Shiraz University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01752153
- Sponsor's protocol ID
- 1929
- Status last verified
- Nov 2012
- First submitted
- 21 Nov 2012
- Last updated
- 19 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunomodulatory Effects of Silymarin in Patients With Beta-Thalassemia Major
- ClinicalTrials.gov ID
- NCT01752153
- Acronym / sponsor ID
- 1929
- Conditions
- Immune Abnormalities
- Keywords
- Focus, immunomodulatory effect, of silymarin, on cell mediated immunity, Beta-Thalassemia, major patients.
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Shiraz University of Medical SciencesUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 19 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Silymarin (Legalon) | Experimental | Drug: 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) | Experimental | Drug: 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Homozygous beta-thalassemia major
- Regularly blood transfusion
- Iron chelation therapy with subcutaneous desferrioxamine (DFO)40.0 mg/Kg/day for 5-7 days/week
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Desferrioxamine, Legalon® (Silymarin)Desferrioxamine (Novartis Pharma AG, Switzerland) at the dose of 40 mg/Kg/day and Legalon® tablets (Madaus Pharma, Italy) | Drug | Combined therapy (Deaferrioxamine+Silymarin (Legalon) |
| Silymarin (Legalon) | Drug | Silymarin (Legalon) |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zahra Amirghofran, PhD study director
Shiraz University of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Desferrioxamine, Legalon® (Silymarin) and Silymarin (Legalon) in people with Immune Abnormalities, run by Shiraz University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in T cell proliferation (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2012.