Clinical trial NCT04292314: Hydroxy Urea, Omega 3, Nigella Sativa,Honey on Oxidative Stress and Iron Chelation in Pediatric Major Thalassemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Iron Overload
Oxidative Stress
Thalassemia Major
Keywords: thymoquinone
omega3
hydroxyurea
pediatric Thalassemia Major
oxidative stress
iron chelation
iron overload
chelation activity of thymoquinone
antioxidant effect of omega3
anti-hemolysis effect of hydroxyurea
Lead sponsor: Beni-Suef University
Sponsor class: OTHER
Collaborators: name: Maternity and Children Hospital, Makkah
name: Beni-Suef Health insurance hospital
name: University of Arizona
First posted: 2020-03-03
Enrollment: 350
Sex: ALL
Minimum age (years): 7
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Four experimental groups, one control group.

Each experimental group receives different experimental treatments plus traditional treatment in the hospital and the control group receives only traditional treatment.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Any case with full manifestation of β-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.

Primary outcomes:
measure: F 2 -isoprostanes pg/mL
timeFrame: 3 months
measure: Total cholesterol Mg/dl
timeFrame: 10 months
measure: HDL cholesterol Mg/dl
timeFrame: 10 months
measure: LDL cholesterol Mg/dl
timeFrame: 10 months
measure: Triglycerides Mg/dl
timeFrame: 10 months
measure: Serum total iron mcg/dL
timeFrame: 10 months
measure: % transferrin saturation
timeFrame: 10 months
measure: C-reactive protein mg/L
timeFrame: 10 months
measure: Serum Ferritin ng/ml
timeFrame: 10 months
measure: Total Iron Binding Capacity (TIBC) mcg/dL
timeFrame: 10 months
measure: hemoglobin (Hbg) g/dL
timeFrame: 10 months
measure: mean corpuscular hemoglobin (MCH) pg/ml
timeFrame: 10 months
measure: leukocytes count μl
timeFrame: 10 months
measure: % Chelation activity Fe+++ - thymoquinone complex
timeFrame: 3 months
measure: % Chelation activity Fe++ - thymoquinone complex
timeFrame: 3 months
measure: Lactic acid dehydrogenase U/L
timeFrame: 10 months
measure: Reticulocyte count %
timeFrame: 10 months
measure: Hb-F level g/dL
timeFrame: 10 months
measure: Reticulocyte absolute count
timeFrame: 10 months
measure: White blood cells count
timeFrame: 10 months
Secondary outcomes:
Other outcomes:
Locations:
city: Banī Suwayf
country: Egypt
facility: Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital
city: Banī Suwayf
country: Egypt
facility: Faculty of Pharmacy, Beni-Suef university
city: Banī Suwayf
country: Egypt
facility: Health insurance hospital
city: Mecca
country: Saudi Arabia
facility: Maternity and Children hospital
Study officials:
affiliation: University of Arizona, College of Pharmacy
name: IVO IBRAHAM [Prof of Pharmacy, Clinical Translational Sciences], Ph.D.
role: STUDY_DIRECTOR
affiliation: Beni-Suef University, Faculty of medicine
name: AHMED A ALBERRY [Assistant prof of clinical pharmacology], Ph.D.
role: STUDY_DIRECTOR
affiliation: Beni-Suef University, Faculty of Pharmacy
name: RAGHDA R SAYED [Lecturer of Clinical Pharmacy], Ph.D.
role: STUDY_DIRECTOR
affiliation: Beni-Suef University, Faculty of Pharmacy
name: MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D Student
role: PRINCIPAL_INVESTIGATOR
affiliation: Beni-Suef university, Faculty of medicine
name: Mohamed H Meabad [Prof of Pediatrics], M.D
role: STUDY_DIRECTOR
affiliation: Beni-Suef Health insurance hospital
name: Ahmed F Mahmoud Hussein, MS.c
role: STUDY_DIRECTOR
References: