Long Term Beta Thalassemia Treatment: Findings From The Extension Period

NCT ID: NCT06490601

Last Updated: 2025-05-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2025-07-01

Brief Summary

The project, titled "Long Term Beta Thalassemia Treatment: Findings From The Extension Period Of Phase 2 Clinical Trial," aims to compare the efficacy and safety of combination therapy (thalidomide and hydroxyurea) versus thalidomide alone. The study, lasting three years, is a Phase 2 single-center, open-label interventional study with a sample size of 30 participants aged 8-35 years. It includes specific inclusion and exclusion criteria for participant selection. Data will be collected through clinical interviews and medical records and analyzed using(Statistical Package for the Social Sciences. This project aims to enhance beta thalassemia treatment strategies, focusing on reducing transfusion dependency and improving patient quality of life.

Detailed Description

Study titled Long Term Beta Thalassemia Treatment: Findings From The Extension Period Of Phase 2 Clinical Trial, conducted at the National Institute of Blood Disease & Bone Marrow Transplantation (NIBD & BMT).

This study focuses on the long-term comparison of combination therapy (thalidomide and hydroxyurea) versus thalidomide alone in treating beta thalassemia. The objective is to evaluate the efficacy and safety of the combination therapy compared to thalidomide alone, with the hypothesis that the combination will be more effective. Beta thalassemia is defined as an autosomal recessive disorder affecting beta-globin production, influenced by genetic modifiers. Key variables include hemoglobin, red blood cells, leukocyte count, reticulocyte count, platelets, lactate dehydrogenase, nucleated red blood cells, ferritin, bilirubin, Serum Glutamate Pyruvate Transaminase, creatinine, transfusion frequency, spleen and liver size, hemoglobin subunit beta [ Homo sapiens (human) ] mutation, and certain polymorphism in gamma globin gene . The study took place at NIBD hospital over three years, designed as a Phase 2 single-center, two-arm open-label interventional study with a sample size of 30 participants using simple randomized sampling. Inclusion criteria are beta thalassemia major/intermediate patients aged 8-35 years, while exclusion criteria include patients with liver dysfunction, married patients, lactating mothers, and those with a history of thrombosis and fits. Data will be collected through clinical interviews and medical record reviews and analyzed using (Statistical Package for the Social Sciences.

Conditions

Fetal Hemoglobin; Beta-Thalassemia; Hemoglobinopathies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

combination therapy (thalidomide and hydroxyurea)

In this group, participants were treated with combination therapy that includes thalidomide and hydroxyurea at the dose of 100mg/day at night with aspirin and 500mg /day respectively.

Group Type: EXPERIMENTAL

thalidomide and hydroxyurea

Intervention Type: DRUG

Thalidomide:

Thalidomide glutarimide is derivation of glutamic acid. Potentiating of fetal hemoglobin expression occurs by up regulation of Erythroid transcription factor and Erythroid Krüppel-like factor expression Furthermore few studies also concluded that thalidomide hypomethylate 27th amino acid in Histone H3 in the gamma globin gene. Initiating cause of this process is suppression of Nuclear factor (kappa-light-chain-enhancer of activated B cells) activation by tumor necrosis factor- alpha Vascular endothelial growth factor , Prostaglandin E2 and inflammatory cytokine.

Hydroxyurea:

Hydroxyurea or hydroxycarbamide (HU) lies in the category of antimetabolite. Mechanism of fetal hemoglobin induction includes increase in erythropoietin and nitric oxide production, apoptosis induction and potentiating in granulocyte cycling activity.

thalidomide alone

In this group, participants were treated with thalidomide at the dose of 100mg/day at night with aspirin.

Group Type: ACTIVE_COMPARATOR

Thalidomide

Intervention Type: DRUG

Thalidomide glutarimide is derivation of glutamic acid. Potentiating of fetal hemoglobin expression occurs by up regulation of Erythroid transcription factor and Erythroid Krüppel-like factor expression Furthermore few studies also concluded that thalidomide hypomethylate 27th amino acid in Histone H3 in the gamma globin gene. Initiating cause of this process is suppression of Nuclear factor (kappa-light-chain-enhancer of activated B cells) activation by tumor necrosis factor -alpha , Vascular endothelial growth factor , Prostaglandin E2 and inflammatory cytokine.

Investigating the impact of thalidomide on transfusion-dependent beta thalassemia patients is essential for discerning its therapeutic efficacy and safety profile.

Interventions

thalidomide and hydroxyurea

Thalidomide:

Thalidomide glutarimide is derivation of glutamic acid. Potentiating of fetal hemoglobin expression occurs by up regulation of Erythroid transcription factor and Erythroid Krüppel-like factor expression Furthermore few studies also concluded that thalidomide hypomethylate 27th amino acid in Histone H3 in the gamma globin gene. Initiating cause of this process is suppression of Nuclear factor (kappa-light-chain-enhancer of activated B cells) activation by tumor necrosis factor- alpha Vascular endothelial growth factor , Prostaglandin E2 and inflammatory cytokine.

Hydroxyurea:

Hydroxyurea or hydroxycarbamide (HU) lies in the category of antimetabolite. Mechanism of fetal hemoglobin induction includes increase in erythropoietin and nitric oxide production, apoptosis induction and potentiating in granulocyte cycling activity.

Intervention Type: DRUG

Thalidomide

Thalidomide glutarimide is derivation of glutamic acid. Potentiating of fetal hemoglobin expression occurs by up regulation of Erythroid transcription factor and Erythroid Krüppel-like factor expression Furthermore few studies also concluded that thalidomide hypomethylate 27th amino acid in Histone H3 in the gamma globin gene. Initiating cause of this process is suppression of Nuclear factor (kappa-light-chain-enhancer of activated B cells) activation by tumor necrosis factor -alpha , Vascular endothelial growth factor , Prostaglandin E2 and inflammatory cytokine.

Investigating the impact of thalidomide on transfusion-dependent beta thalassemia patients is essential for discerning its therapeutic efficacy and safety profile.

Intervention Type: DRUG

Other Intervention Names

combination therapy in beta thalassemia; fetal hemoglobin inducer

Eligibility Criteria

Inclusion Criteria

• Known case of beta thalassemia major/intermediate (transfusion dependent)
• Willing to give informed consent

Exclusion Criteria

• Patients with comorbidities such as liver dysfunction
• Married patients
• Lactating mothers
• History of thrombosis and fits

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Blood and Marrow Transplant (NIBMT), Pakistan

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

National Institute of blood disease and bone marrow transplant

Karachi, Sindh, Pakistan

Countries

Pakistan

References

Henson DE. Loss of p53-immunostaining intensity in breast cancer. J Natl Cancer Inst. 1996 Aug 7;88(15):1015-6. doi: 10.1093/jnci/88.15.1015. No abstract available.

Reference Type: BACKGROUND

PMID: 8683628 (View on PubMed)

Other Identifiers

NIBD/IRB-242/12-2022

Identifier Type: -

Identifier Source: org_study_id