The accumulation of unpaired α-globin chains in β-thalassemia major patients may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, has been known as a potent scavenger of lipid radicals in the red cell membrane of β-thalassemia major patient. By this randomized controlled trial, the investigators would like to evaluate the effects of α-tocopherol in hemolysis and oxidative stress on the red cell membrane of β-thalassemia major.
Full Title of Study: “The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Study Primary Completion Date: July 30, 2017
Background: The accumulation of unpaired α-globin chains in β-thalassemia major patients may clinically create ineffective erythropoiesis, hemolysis, and chronic anemia. Multiple blood transfusions and iron overload cause cellular oxidative damage. However, α-tocopherol, an antioxidant, has been known as a potent scavenger of lipid radicals in the red cell membrane of β-thalassemia major patients. Purpose: To evaluate the effects of α-tocopherol in hemolysis and oxidative stress on the red cell membrane of β-thalassemia major. Methods: In this randomized controlled trial, the investigators allocated subjects in the placebo and α-tocopherol groups. Doses of α-tocopherol were based on the recommendation of Institute of Medicine: 4-8 years old 200 mg/day; 9-13 years old 400 mg/day; 14-18 years old 600 mg/day. Hemolysis, oxidative stress, and antioxidant variables were evaluated before and after 4 weeks of consuming either α-tocopherol or placebo, performed prior to blood transfusions.
- Drug: Alpha-Tocopherol
- all of the subjects in the alpha-tocopherol group received alpha-tocopherol orally, doses adjusted by age for 4 weeks of treatment.
- Drug: Placebo oral tablet
Arms, Groups and Cohorts
- Active Comparator: Alpha-Tocopgerol
- Alpha-Tocopherol supplementation will be given orally for 4 weeks with doses adjusted by age. 5-8 years old: 200 mg daily, 9-13 years old: 400 mg daily and 14-18 years old 600 mg daily.
- Placebo Comparator: Control
- Placebo is the drug with the same shape and color as the alpha-tocopherol supplementation.
Clinical Trial Outcome Measures
- The effects of α-tocopherol in hemolysis marker on the red cell membrane of β-thalassemia major
- Time Frame: 4 weeks
- The plasma haptoglobin and hemolysis as hemolysis marker on alpha-tocopherol treatment were assessed by ELISA using Haptoglobin and Hemopexin kit for human
- The effects of α-tocopherol in oxidative stress marker on the red cell membrane of β-thalassemia major
- Time Frame: 4 weeks
- The malondialdehyde plasma level as oxidative stress marker on alpha-tocopherol treatment was assessed by Spectrophotometry using TBARS method.
- The effects of α-tocopherol in endogenous antioxidant on the red cell membrane of β-thalassemia major
- Time Frame: 4 weeks
- The Glutathione as endogenous antioxidant marker on alpha-tocopherol treatment was assessed by ELISA method by using GT40 for Glutathione kit
Participating in This Clinical Trial
- received frequent transfusions, – iron chelation – aged 5 – 18-year-olds – with no other hematologic disorders – does not consume any other antioxidants or herbal supplements Exclusion Criteria:
- the acute or chronic infection including hepatitis B or hepatitis C, – splenectomy – liver failure – abnormality level of lipid test
Gender Eligibility: All
Minimum Age: 5 Years
Maximum Age: 18 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- Indonesia University
- Provider of Information About this Clinical Study
- Principal Investigator: Nora Sovira, Principal Investigator – Indonesia University
- Overall Official(s)
- Pustika Amalia, Consultant, Principal Investigator, Hematology Oncologist Head Division of Child Health of Universitas Indonesia
Citations Reporting on Results
Fibach E, Rachmilewitz EA. Pathophysiology and treatment of patients with beta-thalassemia – an update. F1000Res. 2017 Dec 20;6:2156. doi: 10.12688/f1000research.12688.1. eCollection 2017. Review.
Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M. Oxidative stress in β-thalassaemia and sickle cell disease. Redox Biol. 2015 Dec;6:226-239. doi: 10.1016/j.redox.2015.07.018. Epub 2015 Aug 1. Review.
Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front Physiol. 2015 Jun 30;6:187. doi: 10.3389/fphys.2015.00187. eCollection 2015. Review.
Schaer CA, Deuel JW, Bittermann AG, Rubio IG, Schoedon G, Spahn DR, Wepf RA, Vallelian F, Schaer DJ. Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage. Cell Death Differ. 2013 Nov;20(11):1569-79. doi: 10.1038/cdd.2013.113. Epub 2013 Aug 30.
Körmöczi GF, Säemann MD, Buchta C, Peck-Radosavljevic M, Mayr WR, Schwartz DW, Dunkler D, Spitzauer S, Panzer S. Influence of clinical factors on the haemolysis marker haptoglobin. Eur J Clin Invest. 2006 Mar;36(3):202-9.
Schaer DJ, Vinchi F, Ingoglia G, Tolosano E, Buehler PW. Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development. Front Physiol. 2014 Oct 28;5:415. doi: 10.3389/fphys.2014.00415. eCollection 2014. Review.
Chow J, Phelan L, Bain BJ. Evaluation of single-tube osmotic fragility as a screening test for thalassemia. Am J Hematol. 2005 Jul;79(3):198-201.
Ghone RA, Kumbar KM, Suryakar AN, Katkam RV, Joshi NG. Oxidative stress and disturbance in antioxidant balance in beta thalassemia major. Indian J Clin Biochem. 2008 Oct;23(4):337-40. doi: 10.1007/s12291-008-0074-7. Epub 2008 Dec 20.
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