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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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 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.
National Institute of blood disease and bone marrow transplant
Karachi, Sindh, Pakistan
hemoglobin levels
Measure the improvement in hemoglobin levels Hemoglobin levels will be assessed using a complete blood count (CBC) test, measured in grams per deciliter (g/dL) of blood. This test is conducted through a venous blood sample, which is then analyzed using an automated hematology analyzer to determine the hemoglobin concentration.
Time frame: 3 years
red blood cell count.
Measure the improvement in red blood cell count. Red blood cell count will be assessed using a complete blood count (CBC) test, measured in millions of cells per microliter (million cells/µL) of blood. This test is conducted through a venous blood sample, analyzed using an automated hematology analyzer to determine the number of red blood cells present.
Time frame: 3 years
leukocyte count
Measure the effect on in leukocyte count Leukocyte count will be assessed using a complete blood count (CBC) test, measured in thousands of cells per microliter (thousand cells/µL) of blood. This test involves analyzing a venous blood sample with an automated hematology analyzer to determine the total number of white blood cells present.
Time frame: 3 years
reticulocyte count
Measure the effect on reticulocyte count Reticulocyte count will be assessed using a complete blood count (CBC) test, measured as a percentage of the total red blood cells or as an absolute number per microliter (µL) of blood. This test involves analyzing a venous blood sample with an automated hematology analyzer, which identifies and quantifies reticulocytes using specific staining techniques.
Time frame: 3 years
Transfusion Frequency:
Document and compare the frequency of blood transfusions required by patients in both treatment arms over the study period. Transfusion frequency will be assessed by recording the number of blood transfusions a patient receives over a specified period, such as weekly, monthly, or annually. This data will be collected from patient medical records and/or transfusion logs, ensuring accurate tracking of each transfusion event.
Time frame: 3 years
Spleen and Liver Size
Measure changes in spleen and liver size as a response to the treatments. Spleen and liver size will be assessed using imaging techniques such as ultrasound.. Measurements will be reported in centimeters (cm), capturing the dimensions of each organ to evaluate any enlargement or abnormalities.
Time frame: 3 years
Serum Ferritin Levels
Evaluate the effectiveness of the combination therapy in reducing serum ferritin levels, indicating decreased iron overload. Serum ferritin levels will be assessed using a blood test, measured in nanograms per milliliter (ng/mL). A venous blood sample will be analyzed in a clinical laboratory using immunoassay techniques to determine the concentration of ferritin, providing an indicator of the body's iron stores.
Time frame: 3 years
Genetic Modifiers:
Analyze the influence of genetic modifiers. Genetic modifiers will be assessed through genetic testing,e.g thalassemia genetic profile focusing on specific genes or genetic variations known to influence the expression or function of proteins related to the condition under study. This analysis helps identify how genetic factors may modify disease progression, treatment response, or other relevant outcomes.
Time frame: 3 years
bilirubin
Monitor and compare changes in biochemical parameters such as bilirubin. Bilirubin levels will be assessed through a blood test, typically measured in milligrams per deciliter (mg/dL). This test analyzes a venous blood sample to determine the concentration of bilirubin, a pigment produced from the breakdown of red blood cells, providing insights into liver function and potential health conditions such as jaundice or liver disease.
Time frame: 3 years
lactate dehydrogenase.
Monitor and compare changes in biochemical parameters such as lactate dehydrogenase. Lactate dehydrogenase (LDH) levels will be assessed through a blood test, measured in units per liter (U/L). This test analyzes a venous blood sample to determine the concentration of LDH, an enzyme involved in cellular metabolism. Elevated LDH levels may indicate tissue damage or disease.
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Time frame: 3 years
Serum Glutamate Pyruvate Transaminase,
Monitor and compare changes in biochemical parameters such as Serum Glutamate Pyruvate Transaminase. Serum Glutamate Pyruvate Transaminase, also known as alanine aminotransferase (ALT), will be assessed through a blood test, measured in units per liter (U/L). This test analyzes a venous blood sample to determine the concentration of ALT, an enzyme primarily found in the liver cells. Elevated ALT levels may indicate liver damage or disease.
Time frame: 3 years
creatinine
Monitor and compare changes in biochemical parameters such as creatinine. Creatinine levels will be assessed through a blood test, typically measured in milligrams per deciliter (mg/dL) or micromoles per liter (µmol/L). This test involves analyzing a venous blood sample to determine the concentration of creatinine, a waste product from muscle metabolism filtered by the kidneys. Monitoring creatinine levels helps evaluate kidney function and detect conditions such as kidney disease or impaired renal function.
Time frame: 3 years