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

Assiut University

Status and phase: Not yet enrolling; Phase 1

Conditions: Thalassemia Major

Treatments: Drug: n-acetylcystine

Study type: Interventional

Funder types: Other

Identifiers

NCT05777733

NAC as antioxidant

Details and patient eligibility

About

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

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 3 to 16 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

100 participants in 1 patient group

N_acetylcystein as antioxidant on iron and frequency of blood transfusion in thalassemia major

Experimental group

Description:

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.

Treatment:

Drug: n-acetylcystine