Hydroxy Urea, Omega 3, Nigella Sativa,Honey on Oxidative Stress and Iron Chelation in Pediatric Major Thalassemia

Oxidative Stress Clinical Trial

Official title:

Impact of Combination Therapy Between Hydroxy Urea, Omega 3, Nigella Sativa and Honey on Antioxidant-oxidant Status and Reduction of Iron Overload in Pediatric Major Thalassemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04292314
• Other study ID #: TQ/Omega-3 on Thalassemia
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 1, 2019
• Est. completion date: January 20, 2021

Study information

• Verified date: January 2021
• Source: Beni-Suef University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 350
• Est. completion date: January 20, 2021
• Est. primary completion date: December 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 15 Years

Eligibility

Inclusion Criteria:

1. Any case with full manifestation of ß-THALASSEMIA major disease

2. #Aged from 7-15 years old

3. # accompanied with ineffective erythropoiesis

4. # with low hemoglobin level

5. # with iron overload

Exclusion Criteria:

1. The presence of any other chronic illness.

2. Patient age>15 years old or < 7 years old.

3. The presence of concomitant myocardial infarction, stroke, acute chest syndrome.

4. The patient suffers from any other type of anemia.

Related Conditions & MeSH terms

• beta-Thalassemia
• Iron Overload
• Oxidative Stress
• Thalassemia
• Thalassemia Major

Intervention

Drug:
• Omega 3
Omega-3 supplementation (300-400mg EPA & 200-300mg DHA) per day for 8 consecutive months up to 10 months
• Nigella Sativa Oil
Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months
• Hydroxyurea
hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months.
• Honey
Natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months.
• 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.

Locations

Country	Name	City	State
Egypt	Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital	Bani Suwayf
Egypt	Faculty of Pharmacy, Beni-Suef university	Bani Suwayf
Egypt	Health insurance hospital	Bani Suwayf
Saudi Arabia	Maternity and Children hospital	Mecca

Sponsors (6)

Lead Sponsor	Collaborator
Beni-Suef University	Beni-Suef Health insurance hospital, College of Pharmacy,Department of Pharmacy Practice,University of Arizona, Department of clinical pharmacy, faculty of pharmacy, Beni-suef univeristy, Maternity and Children Hospital, Makkah, University of Arizona

Countries where clinical trial is conducted

Egypt,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	F 2 -isoprostanes pg/mL	plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay	3 months
Primary	Total cholesterol Mg/dl	Total cholesterol milligrams per deciliter	10 months
Primary	HDL cholesterol Mg/dl	HDL cholesterol milligrams per deciliter	10 months
Primary	LDL cholesterol Mg/dl	LDL cholesterol milligrams per deciliter	10 months
Primary	Triglycerides Mg/dl	Triglycerides milligrams per deciliter	10 months
Primary	Serum total iron mcg/dL	Serum total iron micrograms per decilitre	10 months
Primary	% transferrin saturation	transferrin saturation percentage	10 months
Primary	C-reactive protein mg/L	C-reactive protein milligrams per deciliter	10 months
Primary	Serum Ferritin ng/ml	Serum Ferritin Nanograms per milliliter	10 months
Primary	Total Iron Binding Capacity (TIBC) mcg/dL	Total Iron Binding Capacity micrograms per decilitre	10 months
Primary	hemoglobin (Hbg) g/dL	hemoglobin (Hbg) gram/deciliter	10 months
Primary	mean corpuscular hemoglobin (MCH) pg/ml	mean corpuscular hemoglobin (MCH) Picograms Per Millilitre	10 months
Primary	leukocytes count µl	leukocytes in microliter	10 months
Primary	% Chelation activity Fe+++ - thymoquinone complex	Chelation activity of Ferric - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography - mass spectroscopy analysis	3 months
Primary	% Chelation activity Fe++ - thymoquinone complex	Chelation activity of Ferrous - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography- mass spectroscopy analysis	3 months
Primary	Lactic acid dehydrogenase U/L	Lactic acid dehydrogenase unit per litter	10 months
Primary	Reticulocyte count %	Reticulocyte count percentage	10 months
Primary	Hb-F level g/dL	hemoglobin- F level in gram per deciliter	10 months
Primary	Reticulocyte absolute count	Reticulocyte absolute count in a cubic milliliter of blood	10 months
Primary	White blood cells count	White blood cells count in a cubic milliliter of blood	10 months