Hydroxy Urea, Omega 3, Nigella Sativa,Honey on Oxidative Stress and Iron Chelation in Pediatric Major Thalassemia
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Omega-3 experimental group 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. |
Drug: Omega 3
Omega-3 supplementation (300-400mg EPA & 200-300mg DHA) per day for 8 consecutive months up to 10 months
Drug: Deferoxamine
deferoxamine (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.
Procedure: blood transfusion session
Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.
|
Experimental: Nigella sativa experimental group 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. |
Drug: Nigella Sativa Oil
Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months
Drug: Deferoxamine
deferoxamine (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.
Procedure: blood transfusion session
Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.
|
Experimental: Hydroxyurea experimental group 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. |
Drug: Hydroxyurea
hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months.
Drug: Deferoxamine
deferoxamine (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.
Procedure: blood transfusion session
Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.
|
Experimental: Natural honey experimental group 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. |
Drug: Honey
Natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months.
Other Names:
Drug: Deferoxamine
deferoxamine (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.
Procedure: blood transfusion session
Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.
|
Active Comparator: Ordinary hospital treatment group 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. |
Drug: Deferoxamine
deferoxamine (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.
Procedure: blood transfusion session
Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.
|
Outcome Measures
Primary Outcome Measures
- F 2 -isoprostanes pg/mL [3 months]
plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay
- Total cholesterol Mg/dl [10 months]
Total cholesterol milligrams per deciliter
- HDL cholesterol Mg/dl [10 months]
HDL cholesterol milligrams per deciliter
- LDL cholesterol Mg/dl [10 months]
LDL cholesterol milligrams per deciliter
- Triglycerides Mg/dl [10 months]
Triglycerides milligrams per deciliter
- Serum total iron mcg/dL [10 months]
Serum total iron micrograms per decilitre
- % transferrin saturation [10 months]
transferrin saturation percentage
- 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 Ferric - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography - mass spectroscopy analysis
- % 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
- Reticulocyte absolute count [10 months]
Reticulocyte absolute count in a cubic milliliter of blood
- White blood cells count [10 months]
White blood cells count in a cubic milliliter of blood
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Any case with full manifestation of β-THALASSEMIA major disease
-
#Aged from 7-15 years old
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accompanied with ineffective erythropoiesis
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with low hemoglobin level
-
with iron overload
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital | Banī Suwayf | Egypt | ||
2 | Faculty of Pharmacy, Beni-Suef university | Banī Suwayf | Egypt | ||
3 | Health insurance hospital | Banī Suwayf | Egypt | ||
4 | Maternity and Children hospital | Mecca | Saudi Arabia |
Sponsors and Collaborators
- Beni-Suef University
- Maternity and Children Hospital, Makkah
- Beni-Suef Health insurance hospital
- University of Arizona
Investigators
- Study Director: IVO IBRAHAM [Prof of Pharmacy, Clinical Translational Sciences], Ph.D., University of Arizona, College of Pharmacy
- Study Director: AHMED A ALBERRY [Assistant prof of clinical pharmacology], Ph.D., Beni-Suef University, Faculty of medicine
- Study Director: RAGHDA R SAYED [Lecturer of Clinical Pharmacy], Ph.D., Beni-Suef University, Faculty of Pharmacy
- Principal Investigator: MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D Student, Beni-Suef University, Faculty of Pharmacy
- Study Director: Mohamed H Meabad [Prof of Pediatrics], M.D, Beni-Suef university, Faculty of medicine
- Study Director: Ahmed F Mahmoud Hussein, MS.c, Beni-Suef Health insurance hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TQ/Omega-3 on Thalassemia