The project "Unraveling the Impact of Thalidomide at Diverse Doses in Transfusion Dependent Beta Thalassemia" investigates the safety and efficacy of low-dose thalidomide in managing beta thalassemia, a genetic disorder causing anemia. Conducted over two years at NIBD hospital, the study involves 54 transfusion-dependent patients aged 8-35. The primary objective is to correlate thalidomide doses with disease severity, adverse effects, and treatment response, aiming to optimize treatment strategies and reduce side effects. Data will be collected through clinical interviews and medical record reviews and analyzed using SPSS. Key variables include hemoglobin levels, leukocyte and reticulocyte counts, platelets, liver and spleen size, genetic modifiers, and transfusion frequency. Inclusion criteria are specific to beta thalassemia patients, while exclusion criteria rule out those with liver dysfunction, married patients, lactating mothers, and those with a history of thrombosis or fits.
Thalassemia is an inherited monogenic blood disorder caused by improper synthesis of the hemoglobin chain, inherited in an autosomal recessive pattern. Hemoglobin is essential for oxygen transport from the lungs to body tissues. Initially observed in individuals of Italian descent, thalassemia is characterized by anemia, enlarged spleen, and bone abnormalities. It affects approximately 1.5% of the global population, with 60,000 infants born annually with severe forms such as homozygous alpha thalassemia, beta-thalassemia, and HbH disease. Patients with thalassemia major require frequent blood transfusions and iron chelation therapy to manage iron overload, which can lead to complications like cirrhosis, heart failure, and growth retardation. Iron chelators such as deferasirox, deferiprone, and deferoxamine are used in Pakistan either as solo or combination therapy based on iron levels. Bone marrow transplantation from HLA-identical siblings offers a curative option with high success rates, but non-HLA identical cases are less promising. Emerging therapies like HbF production reactivation, cell therapy, and gene therapy show potential for better management of thalassemia. Beta thalassemia is a prevalent genetic disorder, especially in the Mediterranean, Middle East, and Southeast Asia. It causes reduced hemoglobin production, severe anemia, and dependence on regular blood transfusions, which lead to iron overload and associated complications. Thalidomide, initially marketed as a sedative in 1954 and later withdrawn due to teratogenic effects, has shown efficacy in hematologic disorders. Its potential in beta thalassemia, particularly for reducing transfusion requirements and managing iron overload, remains underexplored. Preliminary studies suggest thalidomide could reduce transfusion needs, but comprehensive dose-dependent research is lacking. This study aims to evaluate the effects of thalidomide at various doses in transfusion-dependent beta thalassemia patients, hypothesizing that optimal dosing can improve disease management and quality of life. Preliminary research indicates thalidomide might reduce transfusion frequency and manage iron overload in beta thalassemia patients. However, detailed dose-dependent studies are necessary. This research aims to fill the gap by exploring thalidomide's benefits and safety profiles at diverse doses, potentially revolutionizing the therapeutic approach to beta thalassemia. The study aims to evaluate the impact of diverse thalidomide doses on reducing transfusion dependency in beta thalassemia patients. Primary objectives include assessing the efficacy of thalidomide in reducing transfusion needs. Secondary objectives involve evaluating the impact on complete blood count, liver function, spleen size, serum ferritin levels, and iron overload, alongside monitoring safety profiles and adverse events. Impact of genetic modifiers on thalidomide and beta thalassemia phenotype will also monitor in this study. The study will be a single-center randomized controlled clinical trial at the National Institute of Blood Disease and Bone Marrow Transplant Hospital in Karachi, Pakistan, specializing in genetic disorders and hematology-oncology. Participants will be divided into treatment (with two dose groups) and control groups, with a total sample size of 54 calculated using OpenEpi. The study will span two years, from May 2024 to May 2026, involving data collection through medical records, interviews, and questionnaires. Ethical approval and informed consent will be obtained, ensuring patient confidentiality and adherence to ethical standards. Data will include patient demographics (age, gender, ethnicity, marital status, weight, height), clinical variables (type of thalassemia, comorbidities, previous treatment), laboratory variables (hemoglobin, leukocyte count, reticulocyte count, platelets, lactate dehydrogenase, ferritin, d-dimer, bilirubin levels, SGPT), genetic modifiers (HBB mutation, XMN polymorphism, BCL11A polymorphism, alpha chain co-inheritance), and others (spleen and liver size, fibroscan, T2 star, transfusion frequency).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Thalidomide is being investigated for its therapeutic efficacy and safety profile in transfusion-dependent beta thalassemia patients. Participants in this arm received thalidomide. Thalidomide was administered orally at a dosage of 5-6mg/kg/day. The medication was taken continuously or on a specified schedule (e.g., daily,) for the duration of the study period, which lasted 2 years. Participants were monitored for adherence to the medication regimen and for any adverse effects throughout the intervention period.
Thalidomide is being investigated for its therapeutic efficacy and safety profile in transfusion-dependent beta thalassemia patients. Participants in this arm received thalidomide. Thalidomide was administered orally at a dosage of 7-8mg/kg/day. The medication was taken continuously or on a specified schedule (e.g., daily,) for the duration of the study period, which lasted 2 years. Participants were monitored for adherence to the medication regimen and for any adverse effects throughout the intervention period.
National Institute of blood disease and bone marrow transplant
Karachi, Sindh, Pakistan
RECRUITINGtransfusion dependency
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: 1 year
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: 2 years
total 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: 2 years
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: 2 years
Platelets
Platelet 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 number of platelets.
Time frame: 2 years
impact of genetic modifiers (e.g., HBB mutation, XMN polymorphism, BCL11A polymorphism, and co-inheritance of alpha chain) on the treatment outcomes with thalidomide.
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: 2 years
Spleen Size
Spleen size will be assessed using imaging techniques such as ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI). Measurements will be reported in centimeters (cm).
Time frame: 2 years
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.
Time frame: 2 years
Serum Ferritin Levels
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: 2 years
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,
Time frame: 2 years
Nucleated red blood cells
Nucleated red blood cells (NRBCs) will be assessed using a complete blood count (CBC) test with a differential, measured as the number of NRBCs per 100 white blood cells (WBCs) or as an absolute number per microliter (µL) of blood. This test involves analyzing a venous blood sample with an automated hematology analyzer, which can differentiate and count NRBCs to provide insights into bone marrow function and potential hematologic disorders.
Time frame: 2 years
D-dimer
D-dimer levels will be assessed through a blood test, typically measured in nanograms per milliliter (ng/mL) or micrograms per liter (µg/L). This test analyzes a venous blood sample to determine the concentration of D-dimer, a fibrin degradation product.
Time frame: 2 years
Total bilirubin
Total bilirubin (TBIL) levels will be assessed through a blood test, measured in milligrams per deciliter (mg/dL). This test analyzes a venous blood sample to determine the total concentration of bilirubin, including both direct (conjugated) and indirect (unconjugated) bilirubin.
Time frame: 2 years
Indirect bilirubin
Indirect bilirubin (IBIL) levels will be assessed through a blood test, measured in milligrams per deciliter (mg/dL). This test analyzes a venous blood sample to determine the concentration of unconjugated bilirubin, which is a byproduct of red blood cell breakdown before it is processed by the liver.
Time frame: 2 years
Fibroscan
FibroScan will be used to assess liver stiffness and steatosis, which can be indicative of liver iron overload. Elevated serum ferritin levels may suggest iron accumulation in the liver, and FibroScan provides a non-invasive method to evaluate the extent of liver fibrosis and fat content.
Time frame: 2 years
T2 star imaging
T2\* (T2 star) magnetic resonance imaging (MRI) will be used to assess liver iron concentration in relation to serum ferritin levels. This imaging technique measures the rate of signal decay in liver tissue, which is inversely correlated with iron content. A shorter T2\* value indicates higher iron concentration. T2\* MRI provides a non-invasive, quantitative assessment of liver iron overload.
Time frame: 2 years
transfusion dependency
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: 2 year
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