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

NCT04292314 | Completed Phase 2

• 1 other identifier: TQ/Omega-3 on Thalassemia
• Study Type: interventional
• Target: 350
• Locations: 2 countries
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (20)

• F 2 -isoprostanes pg/mL

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

  3 months

• Total cholesterol Mg/dl

  Total cholesterol milligrams per deciliter

  10 months

• HDL cholesterol Mg/dl

  HDL cholesterol milligrams per deciliter

  10 months

• LDL cholesterol Mg/dl

  LDL cholesterol milligrams per deciliter

  10 months

• Triglycerides Mg/dl

  Triglycerides milligrams per deciliter

  10 months

• Serum total iron mcg/dL

  Serum total iron micrograms per decilitre

  10 months

• % transferrin saturation

  transferrin saturation percentage

  10 months

• C-reactive protein mg/L

  C-reactive protein milligrams per deciliter

  10 months

• Serum Ferritin ng/ml

  Serum Ferritin Nanograms per milliliter

  10 months

• Total Iron Binding Capacity (TIBC) mcg/dL

  Total Iron Binding Capacity micrograms per decilitre

  10 months

• hemoglobin (Hbg) g/dL

  hemoglobin (Hbg) gram/deciliter

  10 months

• mean corpuscular hemoglobin (MCH) pg/ml

  mean corpuscular hemoglobin (MCH) Picograms Per Millilitre

  10 months

• leukocytes count μl

  leukocytes in microliter

  10 months

• % 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

• % 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

• Lactic acid dehydrogenase U/L

  Lactic acid dehydrogenase unit per litter

  10 months

• Reticulocyte count %

  Reticulocyte count percentage

  10 months

• Hb-F level g/dL

  hemoglobin- F level in gram per deciliter

  10 months

• Reticulocyte absolute count

  Reticulocyte absolute count in a cubic milliliter of blood

  10 months

• White blood cells count

  White blood cells count in a cubic milliliter of blood

  10 months

Study Arms (5)

Omega-3 experimental group

EXPERIMENTAL

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; Drug: Deferoxamine; Procedure: blood transfusion session

Nigella sativa experimental group

EXPERIMENTAL

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; Drug: Deferoxamine; Procedure: blood transfusion session

Hydroxyurea experimental group

EXPERIMENTAL

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; Drug: Deferoxamine; Procedure: blood transfusion session

Natural honey experimental group

EXPERIMENTAL

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; Drug: Deferoxamine; Procedure: blood transfusion session

Ordinary hospital treatment group

ACTIVE COMPARATOR

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; Procedure: blood transfusion session

Interventions

Omega 3 DRUG

Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months

Omega-3 experimental group

Nigella Sativa Oil DRUG

Nigella sativa supplementation (1g black seed oil contain 1% thymoquinone) per day for 8 consecutive months up to 10 months

Nigella sativa experimental group

Hydroxyurea DRUG

hydroxyurea medication (5 to 15mg/kg) per day for 8 consecutive months up to 10 months.

Hydroxyurea experimental group

Honey DRUG

Natural honey(2.5 mg/kg dissolved in 250 ml water) per day for 8 consecutive months up to 10 months.

Also known as: Natural honey formulation

Natural honey experimental group

Deferoxamine DRUG

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.

Hydroxyurea experimental group; Natural honey experimental group; Nigella sativa experimental group; Omega-3 experimental group; Ordinary hospital treatment group

blood transfusion session PROCEDURE

Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.

Hydroxyurea experimental group; Natural honey experimental group; Nigella sativa experimental group; Omega-3 experimental group; Ordinary hospital treatment group

Eligibility Criteria

• Age: 7 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Any case with full manifestation of β-THALASSEMIA major disease
• #Aged from 7-15 years old
• \# accompanied with ineffective erythropoiesis
• \# with low hemoglobin level
• \# with iron overload

You may not qualify if:

• The presence of any other chronic illness.
• Patient age\>15 years old or \< 7 years old.
• The presence of concomitant myocardial infarction, stroke, acute chest syndrome.
• The patient suffers from any other type of anemia.

Sponsors & Collaborators

• Beni-Suef University: lead
• Maternity and Children Hospital, Makkah: collaborator
• Beni-Suef Health insurance hospital: collaborator
• University of Arizona: collaborator

Study Sites (4)

Faculty of medicine, Beni-suef univeristy - Beni-Suef university hospital

Banī Suwayf, Egypt

Location

Faculty of Pharmacy, Beni-Suef university

Banī Suwayf, Egypt

Location

Health insurance hospital

Banī Suwayf, Egypt

Location

Maternity and Children hospital

Mecca, Saudi Arabia

Location

MeSH Terms

Conditions

Iron Overload; beta-Thalassemia

Interventions

Docosahexaenoic Acids; Nigella sativa oil; Hydroxyurea; Honey; Deferoxamine

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Urea; Amides; Organic Chemicals; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids

Study Officials

• 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

  STUDY DIRECTOR

• MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D Student

  Beni-Suef University, Faculty of Pharmacy

  PRINCIPAL INVESTIGATOR

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.Mohamed Medhat Abdelwahab Gamaleldin

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 3, 2020
• Study Start: November 1, 2019
• Primary Completion: December 20, 2020
• Study Completion: January 20, 2021
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

EG (3); SA (1)