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

Sponsor
Beni-Suef University (Other)
Overall Status
Completed
CT.gov ID
NCT04292314
Collaborator
Maternity and Children Hospital, Makkah (Other), Beni-Suef Health insurance hospital (Other), University of Arizona (Other)
350
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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

Study Type:
Interventional
Actual Enrollment :
350 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.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 :
Nov 1, 2019
Actual Primary Completion Date :
Dec 20, 2020
Actual Study Completion Date :
Jan 20, 2021

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:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. F 2 -isoprostanes pg/mL [3 months]

      plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay

    2. Total cholesterol Mg/dl [10 months]

      Total cholesterol milligrams per deciliter

    3. HDL cholesterol Mg/dl [10 months]

      HDL cholesterol milligrams per deciliter

    4. LDL cholesterol Mg/dl [10 months]

      LDL cholesterol milligrams per deciliter

    5. Triglycerides Mg/dl [10 months]

      Triglycerides milligrams per deciliter

    6. Serum total iron mcg/dL [10 months]

      Serum total iron micrograms per decilitre

    7. % transferrin saturation [10 months]

      transferrin saturation percentage

    8. C-reactive protein mg/L [10 months]

      C-reactive protein milligrams per deciliter

    9. Serum Ferritin ng/ml [10 months]

      Serum Ferritin Nanograms per milliliter

    10. Total Iron Binding Capacity (TIBC) mcg/dL [10 months]

      Total Iron Binding Capacity micrograms per decilitre

    11. hemoglobin (Hbg) g/dL [10 months]

      hemoglobin (Hbg) gram/deciliter

    12. mean corpuscular hemoglobin (MCH) pg/ml [10 months]

      mean corpuscular hemoglobin (MCH) Picograms Per Millilitre

    13. leukocytes count μl [10 months]

      leukocytes in microliter

    14. % 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

    15. % 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

    16. Lactic acid dehydrogenase U/L [10 months]

      Lactic acid dehydrogenase unit per litter

    17. Reticulocyte count % [10 months]

      Reticulocyte count percentage

    18. Hb-F level g/dL [10 months]

      hemoglobin- F level in gram per deciliter

    19. Reticulocyte absolute count [10 months]

      Reticulocyte absolute count in a cubic milliliter of blood

    20. White blood cells count [10 months]

      White blood cells count in a cubic milliliter of blood

    Eligibility Criteria

    Criteria

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

    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.
    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:
    Mar 3, 2020
    Last Update Posted:
    Jan 27, 2021
    Last Verified:
    Jan 1, 2021
    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, Dr.Mohamed Medhat Abdelwahab Gamaleldin, Beni-Suef University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 27, 2021