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

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ClinicalTrials.gov Identifier: NCT04292314
Recruitment Status : Recruiting
First Posted : March 3, 2020
Last Update Posted : March 3, 2020
Sponsor:
Collaborators:
Maternity and Children Hospital, Makkah
Department of clinical pharmacy, faculty of pharmacy, Beni-suef univeristy
Benisuef university hospital
University of Arizona
College of Pharmacy,Department of Pharmacy Practice,University of Arizona
Information provided by (Responsible Party):
Mohamed Medhat Abdelwahab Gamaleldin, 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.

Condition or disease Intervention/treatment Phase
Iron Overload Oxidative Stress Thalassemia Major Drug: Omega 3 Drug: Nigella Sativa Oil Drug: Hydroxyurea Drug: Honey Drug: Deferoxamine Procedure: blood transfusion session 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
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
Actual Study Start Date : November 1, 2019
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : November 2020


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 Name: Natural honey formulation

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.




Primary Outcome Measures :
  1. F 2 -isoprostanes pg/mL [ Time Frame: 3 months ]
    plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay

  2. Total cholesterol Mg/dl [ Time Frame: 10 months ]
    Total cholesterol milligrams per deciliter

  3. HDL cholesterol Mg/dl [ Time Frame: 10 months ]
    HDL cholesterol milligrams per deciliter

  4. LDL cholesterol Mg/dl [ Time Frame: 10 months ]
    LDL cholesterol milligrams per deciliter

  5. Triglycerides Mg/dl [ Time Frame: 10 months ]
    Triglycerides milligrams per deciliter

  6. Serum total iron mcg/dL [ Time Frame: 10 months ]
    Serum total iron micrograms per decilitre

  7. % transferrin saturation [ Time Frame: 10 months ]
    transferrin saturation percentage

  8. C-reactive protein mg/L [ Time Frame: 10 months ]
    C-reactive protein milligrams per deciliter

  9. Serum Ferritin ng/ml [ Time Frame: 10 months ]
    Serum Ferritin Nanograms per milliliter

  10. Total Iron Binding Capacity (TIBC) mcg/dL [ Time Frame: 10 months ]
    Total Iron Binding Capacity micrograms per decilitre

  11. hemoglobin (Hbg) g/dL [ Time Frame: 10 months ]
    hemoglobin (Hbg) gram/deciliter

  12. mean corpuscular hemoglobin (MCH) pg/ml [ Time Frame: 10 months ]
    mean corpuscular hemoglobin (MCH) Picograms Per Millilitre

  13. leukocytes count μl [ Time Frame: 10 months ]
    leukocytes in microliter

  14. % Chelation activity Fe+++ - thymoquinone complex [ Time Frame: 3 months ]
    Chelation activity of Ferric - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography - mass spectroscopy analysis

  15. % Chelation activity Fe++ - thymoquinone complex [ Time Frame: 3 months ]
    Chelation activity of Ferrous - thymoquinone complex in percentage measured by high pressure liquid chromatography coupled with gaschromatography- mass spectroscopy analysis

  16. Lactic acid dehydrogenase U/L [ Time Frame: 10 months ]
    Lactic acid dehydrogenase unit per litter

  17. Reticulocyte count % [ Time Frame: 10 months ]
    Reticulocyte count percentage

  18. Hb-F level g/dL [ Time Frame: 10 months ]
    hemoglobin- F level in gram per deciliter

  19. Reticulocyte absolute count [ Time Frame: 10 months ]
    Reticulocyte absolute count in a cubic milliliter of blood

  20. White blood cells count [ Time Frame: 10 months ]
    White blood cells count in a cubic milliliter of blood



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Ages Eligible for Study:   7 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04292314


Contacts
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Contact: MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D Student 00201110188554 dr.mohmedhat@gmail.com

Locations
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Egypt
Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital Recruiting
Banī Suwayf, Egypt
Contact: MOHAMED H MEABAD, M.D    00201001310287    M1hmeabed2@yahoo.com   
Contact: AHMED A ALBERRY, Ph.D.    00201000425922    berry_ahmed@yahoo.com   
Faculty of Pharmacy, Beni-Suef university Recruiting
Banī Suwayf, Egypt
Contact: MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D.student    00201110188554    dr.mohmedhat@gmail.com   
Contact: RAGHDA R SAYED, Ph.D.    00201010647666    smartraro@yahoo.com   
Saudi Arabia
Maternity and Children hospital Recruiting
Mecca, Saudi Arabia
Contact: MOHAMED M ABDELWAHAB GAMALELDIN, PhD student    00201110188554    dr.mohmedhat@gmail.com   
Contact: HASSAN Masmali [consultant of Pediatrics], M.D    00966555352442    masmaly@gmail.com   
Sponsors and Collaborators
Beni-Suef University
Maternity and Children Hospital, Makkah
Department of clinical pharmacy, faculty of pharmacy, Beni-suef univeristy
Benisuef university hospital
University of Arizona
College of Pharmacy,Department of Pharmacy Practice,University of Arizona
Investigators
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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

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Responsible Party: Mohamed Medhat Abdelwahab Gamaleldin, Dr.Mohamed Medhat Abdelwahab Gamaleldin, Beni-Suef University
ClinicalTrials.gov Identifier: NCT04292314    
Other Study ID Numbers: TQ/Omega-3 on Thalassemia
First Posted: March 3, 2020    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mohamed Medhat Abdelwahab Gamaleldin, Beni-Suef University:
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
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Iron Overload
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Iron
Hydroxyurea
Antioxidants
Deferoxamine
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents