Effects of Hydroxyurea and Metformin in Transfusion Dependent Beta-Thalassemia

Summary

This clinical trial aims to evaluate and compare the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major and correlate responders/non-responders with the single nucleotide polymorphism mutations (SNPs) by DNA analysis. The main question to answer is: * Is there a significant difference in the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major? Participants will be divided into two treatment groups. Participants of group A will receive Tab. Metformin 500mg/dose twice daily orally for one year. Participants of group B will receive Tab. Hydroxyurea 10-20mg/kg once daily orally for one year. At the end of the study, Investigators will compare the effects and safety of hydroxyurea and metformin in transfusion-dependent beta-thalassemia major and correlate responders/non-responders with the single nucleotide polymorphism mutations (SNPs) by DNA analysis.

Timeline

Start

2024-09-16

Primary completion

2026-02-09

Completion

2026-02-09

Publications

• Background ElTagui M, El-Ghamrawy M, AlDeeb SK, Nassim MS. Metformin as a Fetal Hemoglobin Inducer in Non-transfusion Dependent Thalassemia Patients. Indian J Hematol Blood Transfus. 2024 Jan;40(1):68-73. doi: 10.1007/s12288-023-01662-1. Epub 2023 May 5.
• Background Yasara N, Wickramarathne N, Mettananda C, Silva I, Hameed N, Attanayaka K, Rodrigo R, Wickramasinghe N, Perera L, Manamperi A, Premawardhena A, Mettananda S. A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent beta-thalassaemia. Sci Rep. 2022 Feb 17;12(1):2752. doi: 10.1038/s41598-022-06774-8.
• Background Arian M, Mirmohammadkhani M, Ghorbani R, Soleimani M. Health-related quality of life (HRQoL) in beta-thalassemia major (beta-TM) patients assessed by 36-item short form health survey (SF-36): a meta-analysis. Qual Life Res. 2019 Feb;28(2):321-334. doi: 10.1007/s11136-018-1986-1. Epub 2018 Sep 7.
• Background Yasara N, Premawardhena A, Mettananda S. A comprehensive review of hydroxyurea for beta-haemoglobinopathies: the role revisited during COVID-19 pandemic. Orphanet J Rare Dis. 2021 Mar 1;16(1):114. doi: 10.1186/s13023-021-01757-w.
• Background Mu W, Liang G, Feng Y, Jiang Y, Qu F. The Potential Therapeutic Role of Metformin in Diabetic and Non-Diabetic Bone Impairment. Pharmaceuticals (Basel). 2022 Oct 17;15(10):1274. doi: 10.3390/ph15101274.
• Background Zhang Y, Wang H, Xiao H. Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC. Int J Mol Sci. 2021 May 9;22(9):5016. doi: 10.3390/ijms22095016.
• Background Gluba-Brzozka A, Franczyk B, Rysz-Gorzynska M, Rokicki R, Koziarska-Rosciszewska M, Rysz J. Pathomechanisms of Immunological Disturbances in beta-Thalassemia. Int J Mol Sci. 2021 Sep 7;22(18):9677. doi: 10.3390/ijms22189677.

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