The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major

Oxidative Stress Clinical Trial

Official title:

The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03948737
• Other study ID #: NSovira
• Status: Completed
• Phase: N/A
• Start date: December 30, 2016
• Est. completion date: August 1, 2017

Study information

• Verified date: May 2019
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: August 1, 2017
• Est. primary completion date: July 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 18 Years

Eligibility

Inclusion Criteria:

• 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

Related Conditions & MeSH terms

• Beta Thalassemia Major Anemia
• beta-Thalassemia
• Hemolysis
• Oxidative Stress
• Thalassemia

Intervention

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.
• Placebo oral tablet

Locations

Country	Name	City	State
Indonesia	Thalassemia Centre Kiara RSUP Dr.CiptoMangunkusumo	Jakarta Pusat	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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: 10.103 — View Citation

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. Re — View Citation

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. — View Citation

Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M. Oxidative stress in ß-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The effects of a-tocopherol in hemolysis marker on the red cell membrane of ß-thalassemia major	The plasma haptoglobin and hemolysis as hemolysis marker on alpha-tocopherol treatment were assessed by ELISA using Haptoglobin and Hemopexin kit for human	4 weeks
Secondary	The effects of a-tocopherol in oxidative stress marker on the red cell membrane of ß-thalassemia major	The malondialdehyde plasma level as oxidative stress marker on alpha-tocopherol treatment was assessed by Spectrophotometry using TBARS method.	4 weeks
Secondary	The effects of a-tocopherol in endogenous antioxidant on the red cell membrane of ß-thalassemia major	The Glutathione as endogenous antioxidant marker on alpha-tocopherol treatment was assessed by ELISA method by using GT40 for Glutathione kit	4 weeks

External Links

•   Drug information of alpha-Tocopherol