Hydroxy Urea, Omega 3, Nigella Sativa,Honey on Oxidative Stress and Iron Chelation in Pediatric Major Thalassemia
- Conditions
- Iron OverloadOxidative StressThalassemia Major
- Interventions
- Drug: Nigella Sativa OilProcedure: blood transfusion session
- Registration Number
- NCT04292314
- Lead Sponsor
- Beni-Suef University
- Brief Summary
The aim of the present study is evaluating the strength of combination therapy of hydroxy urea, omega 3, nigella sativa and honey on antioxidant-oxidant status (OXIDATIVE STRESS) in response to reactive oxygen species production (LIPID PEROXIDATION) and their effect on iron intoxication (IRON CHELATION) in pediatric major thalassemia.
- Detailed Description
Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body. In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots. Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as Cooley's anemia) and thalassemia intermedia. Of the two types, thalassemia major is more severe.
Beta-thalassemia syndromes are a group of hereditary blood disorders. It is characterized by reduced beta globin chain synthesis, resulting in reduced Hb in red blood cells (RBC), decreased RBC production and anemia.
Homozygotes for beta-thalassemia may develop either thalassemia major or thalassemia intermedia. Individuals with thalassemia major usually come to medical attention within the first 2 years and require regular blood transfusion to survive.
Affected infants with thalassemia major fail to thrive and become progressively pale. Feeding problems, diarrhea, irritability, recurrent bouts of fever, and enlargement of the abdomen, caused by splenomegaly, may occur. If a regular transfusion program that maintains a minimum Hb concentration of 95-105 g/L is initiated, then growth and development are normal until the age of 10-11 years. After the age of 10-11 years, affected individuals are at risk of developing severe complications related to posttransfusional iron overload, depending on their compliance with chelation therapy.
Complications of iron overload include growth retardation and failure of sexual maturation and also those complications observed in adults with hemachromatosis -associated hereditary hemochromatosis (HH): involvement of the heart (dilated myocardiopathy and pericarditis), liver (chronic hepatitis, fibrosis, and cirrhosis), and endocrine glands (resulting in diabetes mellitus and insufficiency of the parathyroid, thyroid, pituitary, and, less commonly, adrenal glands).
The underlying basis of b-thalassemia pathology is the diminished b-globin synthesis leading to a-globin accumulation and premature apoptotic destruction of erythroblasts, causing oxidative stress-induced ineffective erythropoiesis.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 350
- Any case with full manifestation of β-THALASSEMIA major disease
- #Aged from 7-15 years old
-
accompanied with ineffective erythropoiesis
-
with low hemoglobin level
-
with iron overload
- The presence of any other chronic illness.
- Patient age>15 years old or < 7 years old.
- The presence of concomitant myocardial infarction, stroke, acute chest syndrome.
- The patient suffers from any other type of anemia.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Omega-3 experimental group blood transfusion session 50 patients from each participating hospital that will receive Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Nigella sativa experimental group Nigella Sativa Oil 50 patients from each participating hospital that will receive Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Nigella sativa experimental group blood transfusion session 50 patients from each participating hospital that will receive Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Hydroxyurea experimental group blood transfusion session 50 patients from each participating hospital that will receive hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Natural honey experimental group blood transfusion session 50 patients from each participating hospital that will receive natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Ordinary hospital treatment group blood transfusion session 50 patients from each participating hospital that will receive the ordinary treatment of iron chelator agent of deferoxamine or deferasirox (SubQ infusion: 20 to 40 mg/kg/day over 8 to 12 hours, 6 to 7 nights per week, maximum daily dose: 40 mg/kg/day)for 8 consecutive months up to 10 months. in addition to iron chelator agent, this group receive regular blood transfusion session. Omega-3 experimental group Omega 3 50 patients from each participating hospital that will receive Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Omega-3 experimental group Deferoxamine 50 patients from each participating hospital that will receive Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Nigella sativa experimental group Deferoxamine 50 patients from each participating hospital that will receive Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months. in addition to experimental treatment this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods till efficacy of experimental treatment proved. Hydroxyurea experimental group Hydroxyurea 50 patients from each participating hospital that will receive hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Hydroxyurea experimental group Deferoxamine 50 patients from each participating hospital that will receive hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Natural honey experimental group Honey 50 patients from each participating hospital that will receive natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Natural honey experimental group Deferoxamine 50 patients from each participating hospital that will receive natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of deferoxamine/deferasirox plus regular blood transfusion with dose de-escalation methods until the efficacy of experimental treatment proved. Ordinary hospital treatment group Deferoxamine 50 patients from each participating hospital that will receive the ordinary treatment of iron chelator agent of deferoxamine or deferasirox (SubQ infusion: 20 to 40 mg/kg/day over 8 to 12 hours, 6 to 7 nights per week, maximum daily dose: 40 mg/kg/day)for 8 consecutive months up to 10 months. in addition to iron chelator agent, this group receive regular blood transfusion session.
- Primary Outcome Measures
Name Time Method Reticulocyte absolute count 10 months Reticulocyte absolute count in a cubic milliliter of blood
HDL cholesterol Mg/dl 10 months HDL cholesterol milligrams per deciliter
LDL cholesterol Mg/dl 10 months LDL cholesterol milligrams per deciliter
Total cholesterol Mg/dl 10 months Total cholesterol milligrams per deciliter
% Chelation activity Fe+++ - thymoquinone complex 3 months Chelation activity of Ferric - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography - mass spectroscopy analysis
% transferrin saturation 10 months transferrin saturation percentage
F 2 -isoprostanes pg/mL 3 months plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay
Serum total iron mcg/dL 10 months Serum total iron micrograms per decilitre
C-reactive protein mg/L 10 months C-reactive protein milligrams per deciliter
Serum Ferritin ng/ml 10 months Serum Ferritin Nanograms per milliliter
Total Iron Binding Capacity (TIBC) mcg/dL 10 months Total Iron Binding Capacity micrograms per decilitre
hemoglobin (Hbg) g/dL 10 months hemoglobin (Hbg) gram/deciliter
mean corpuscular hemoglobin (MCH) pg/ml 10 months mean corpuscular hemoglobin (MCH) Picograms Per Millilitre
leukocytes count μl 10 months leukocytes in microliter
% Chelation activity Fe++ - thymoquinone complex 3 months Chelation activity of Ferrous - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography- mass spectroscopy analysis
Lactic acid dehydrogenase U/L 10 months Lactic acid dehydrogenase unit per litter
Reticulocyte count % 10 months Reticulocyte count percentage
Hb-F level g/dL 10 months hemoglobin- F level in gram per deciliter
Triglycerides Mg/dl 10 months Triglycerides milligrams per deciliter
White blood cells count 10 months White blood cells count in a cubic milliliter of blood
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (4)
Maternity and Children hospital
🇸🇦Mecca, Saudi Arabia
Health insurance hospital
🇪🇬Banī Suwayf, Egypt
Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital
🇪🇬Banī Suwayf, Egypt
Faculty of Pharmacy, Beni-Suef university
🇪🇬Banī Suwayf, Egypt