NAC Effect on Iron Overload and Blood Transfusion in β-thalassemia Major

Study Overview
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Brief Summary
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The effect of N_acetylcystein as an antioxidant on iron overload and frequency of blood transfusion in β-thalassemia major patients at Assiut Childern Hospital University And its cosubmitted for partial fulfillment of master degree in Pediatrics

Detailed Description
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Beta thalassemia major it menifests after 6 months of life by severe anemia requiring life-long blood transfusion,which is the the gold standard therapy causing many complications including iron overload which associated to a certain extent with the generation of labile iron in the pathological red blood cell (RBC). The appearance of such forms of iron at the inner and outer cell surfaces exposes the cell to formation of reactive oxygen species (ROS),particularly the hydroxyl radical (·OH) serving as a Fenton reagent, Hydroxyl radical facilitated by membraneassociated iron might be particularly harmful because radical generation would be relatively sequestered from the cell antioxidant capacity and occur directly adjacent to lipid and protein membrane components exceeding cellular defense capacities causing oxidtive stress with prematre cell damage which is the main pathophysiological process in thalassemia . the fact that iron plays a major role in the generation of ROS implies that iron chelators can also serve as antioxidants. Obviously, chelation of iron is one of the major therapeutic goals in thalassemia. Consequently, the orally administered iron chelator deferiprone was able to remove free iron from β- thalassemic red cell membranes in a dose-related fashion, Deferiprone alleviated membrane damage possibly mediated by catalytic iron, such as In a few patients with Hb E/β thalassemia in Thailand, following administration of deferiprone alone for an average of 50 weeks, Hb levels increased concomitant with a decrease in transfusion requirement One possible explanation for this finding is that deferiprone acted like an antioxidant by removing excess free iron from the cells and, as a result, ROS generation was decreased. However, the antioxidant effect of this iron chelator by itself was not sufficient to neutralize the damage induced by ROS Moreover, oral administration of other antioxidant such as vitamin E, which is a lipid antioxidant, exhibited improvement in oxidant-antioxidant balance in the plasma . Another antioxidant that acts primarily on proteins is n_acetylcysteine, which improved certain parameters resulting from oxidative damage to sickle RBCs. here we will give the N_acetylcysteine orally in dose 10mg\kg\day to the thalassemic patients for 6 months and observing its effect as antioxidant on iron overload and the frequency in blood transfusion The ultimate purpose of all these observations is to try to design a combination of antioxidants consisting of an iron chelator, such as deferiprone, vitamin E as antioxidant for the lipids, and N-acetylcysteine as antioxidant for the proteins to decrease the deleterious effect of ORS.

Official Title
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The Effect of N_acetylcystein as an Antioxidant on Iron Overload and Frequency of Blood Transfusion in β-thalassemia Major Patients at Assiut Childern Hospital University

Conditions
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Thalassemia Major

Intervention / Treatment
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* Drug: n-acetylcystine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: thalassemia major children . On oral iron chelation . Exclusion Criteria: change in the dose of iron chelation within 3 months before enrollement or during study period . Liver impairment Renal impairment patients not adeherent to therapy

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 16 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: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: N-acetylcystein in dose 10mg /kg single oral dose will be given for 6 months
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N_acetylcystein as antioxidant on iron and frequency of blood transfusion in thalassemia major<br>N_acetylcystein administration on single oral dose 10mg /kg for 6 months and it's effect on iron and frequency of blood transfusion before and after its use. | Drug: n-acetylcystine<br>* Single daily oral administration of N_acetylcystein on dose 10mg /kg/day<br>* Other names: acetylcystein;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum ferritin level | Measuring serum ferritin level (mg/dl) before and after 6 months of acetylcystein administration. | 6 months from the baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N_acetylcystein antioxidant effect