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

• ClinicalTrials.gov Identifier: NCT04292314
• Recruitment Status: Completed
• First Posted: March 3, 2020
• Last Update Posted: January 27, 2021
• Sponsor: Beni-Suef University
• Collaborators: Maternity and Children Hospital, Makkah; Beni-Suef Health insurance hospital; University of Arizona
• Information provided by (Responsible Party): Mohamed Medhat Abdelwahab Gamaleldin, Beni-Suef University

Tracking Information

• First Submitted Date: February 28, 2020
• First Posted Date: March 3, 2020
• Last Update Posted Date: January 27, 2021
• Actual Study Start Date: November 1, 2019
• Actual Primary Completion Date: December 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2020)

• F 2 -isoprostanes pg/mL [ Time Frame: 3 months ]
  plasma F 2 -isoprostanes Picograms Per Millilitre measured by high pressure liquid chromatography assay
• Total cholesterol Mg/dl [ Time Frame: 10 months ]
  Total cholesterol milligrams per deciliter
• HDL cholesterol Mg/dl [ Time Frame: 10 months ]
  HDL cholesterol milligrams per deciliter
• LDL cholesterol Mg/dl [ Time Frame: 10 months ]
  LDL cholesterol milligrams per deciliter
• Triglycerides Mg/dl [ Time Frame: 10 months ]
  Triglycerides milligrams per deciliter
• Serum total iron mcg/dL [ Time Frame: 10 months ]
  Serum total iron micrograms per decilitre
• % transferrin saturation [ Time Frame: 10 months ]
  transferrin saturation percentage
• C-reactive protein mg/L [ Time Frame: 10 months ]
  C-reactive protein milligrams per deciliter
• Serum Ferritin ng/ml [ Time Frame: 10 months ]
  Serum Ferritin Nanograms per milliliter
• Total Iron Binding Capacity (TIBC) mcg/dL [ Time Frame: 10 months ]
  Total Iron Binding Capacity micrograms per decilitre
• hemoglobin (Hbg) g/dL [ Time Frame: 10 months ]
  hemoglobin (Hbg) gram/deciliter
• mean corpuscular hemoglobin (MCH) pg/ml [ Time Frame: 10 months ]
  mean corpuscular hemoglobin (MCH) Picograms Per Millilitre
• leukocytes count μl [ Time Frame: 10 months ]
  leukocytes in microliter
• % 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
• % 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
• Lactic acid dehydrogenase U/L [ Time Frame: 10 months ]
  Lactic acid dehydrogenase unit per litter
• Reticulocyte count % [ Time Frame: 10 months ]
  Reticulocyte count percentage
• Hb-F level g/dL [ Time Frame: 10 months ]
  hemoglobin- F level in gram per deciliter
• Reticulocyte absolute count [ Time Frame: 10 months ]
  Reticulocyte absolute count in a cubic milliliter of blood
• White blood cells count [ Time Frame: 10 months ]
  White blood cells count in a cubic milliliter of blood

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

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

Condition

• Iron Overload
• Oxidative Stress
• 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
• 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: Hydroxyurea
  hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months.
• 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.

Study Arms

• 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.

  Interventions:

  • Drug: Omega 3
  • Drug: Deferoxamine
  • Procedure: blood transfusion session
• 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.

  Interventions:

  • Drug: Nigella Sativa Oil
  • Drug: Deferoxamine
  • Procedure: blood transfusion session
• 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.

  Interventions:

  • Drug: Hydroxyurea
  • Drug: Deferoxamine
  • Procedure: blood transfusion session
• 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.

  Interventions:

  • Drug: Honey
  • Drug: Deferoxamine
  • Procedure: blood transfusion session
• 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.

  Interventions:

  • Drug: Deferoxamine
  • Procedure: blood transfusion session

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 10, 2020): 350
• Original Estimated Enrollment (submitted: February 28, 2020): 500
• Actual Study Completion Date: January 20, 2021
• Actual Primary Completion Date: December 20, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 15 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt, Saudi Arabia

Administrative Information

• NCT Number: NCT04292314
• Other Study ID Numbers: TQ/Omega-3 on Thalassemia
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mohamed Medhat Abdelwahab Gamaleldin, Beni-Suef University
• Original Responsible Party: Same as current
• Current Study Sponsor: Beni-Suef University
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: Beni-Suef University
• Verification Date: January 2021