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

NCT ID: NCT04292314

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2021-01-20

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.

Conditions

Iron Overload; Oxidative Stress; Thalassemia Major

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Omega 3

Intervention Type: DRUG

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

Deferoxamine

Intervention Type: 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.

blood transfusion session

Intervention Type: PROCEDURE

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

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.

Group Type: EXPERIMENTAL

Nigella Sativa Oil

Intervention Type: DRUG

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

Deferoxamine

Intervention Type: 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.

blood transfusion session

Intervention Type: PROCEDURE

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

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.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

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

Deferoxamine

Intervention Type: 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.

blood transfusion session

Intervention Type: PROCEDURE

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

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.

Group Type: EXPERIMENTAL

Honey

Intervention Type: DRUG

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

Deferoxamine

Intervention Type: 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.

blood transfusion session

Intervention Type: PROCEDURE

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

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.

Group Type: ACTIVE_COMPARATOR

Deferoxamine

Intervention Type: 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.

blood transfusion session

Intervention Type: PROCEDURE

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

Interventions

Omega 3

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

Intervention Type: DRUG

Nigella Sativa Oil

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

Intervention Type: DRUG

Hydroxyurea

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

Intervention Type: DRUG

Honey

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

Intervention Type: 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.

Intervention Type: DRUG

blood transfusion session

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

Intervention Type: PROCEDURE

Other Intervention Names

Natural honey formulation

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.

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maternity and Children Hospital, Makkah

OTHER

Sponsor Role: collaborator

Beni-Suef Health insurance hospital

UNKNOWN

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: collaborator

Beni-Suef University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Medhat Abdelwahab Gamaleldin

Dr.Mohamed Medhat Abdelwahab Gamaleldin

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

IVO IBRAHAM [Prof of Pharmacy, Clinical Translational Sciences], Ph.D.

Role: STUDY_DIRECTOR

University of Arizona, College of Pharmacy

AHMED A ALBERRY [Assistant prof of clinical pharmacology], Ph.D.

Role: STUDY_DIRECTOR

Beni-Suef University, Faculty of medicine

RAGHDA R SAYED [Lecturer of Clinical Pharmacy], Ph.D.

Role: STUDY_DIRECTOR

Beni-Suef University, Faculty of Pharmacy

MOHAMED M ABDELWAHAB GAMALELDIN, Ph.D Student

Role: PRINCIPAL_INVESTIGATOR

Beni-Suef University, Faculty of Pharmacy

Mohamed H Meabad [Prof of Pediatrics], M.D

Role: STUDY_DIRECTOR

Beni-Suef university, Faculty of medicine

Ahmed F Mahmoud Hussein, MS.c

Role: STUDY_DIRECTOR

Beni-Suef Health insurance hospital

Locations

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

Banī Suwayf, , Egypt

Faculty of Pharmacy, Beni-Suef university

Banī Suwayf, , Egypt

Health insurance hospital

Banī Suwayf, , Egypt

Maternity and Children hospital

Mecca, , Saudi Arabia

Countries

Egypt; Saudi Arabia

Other Identifiers

TQ/Omega-3 on Thalassemia

Identifier Type: -

Identifier Source: org_study_id