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

• ClinicalTrials.gov Identifier: NCT03948737
• Recruitment Status: Completed
• First Posted: May 14, 2019
• Last Update Posted: May 14, 2019
• Sponsor: Indonesia University
• Information provided by (Responsible Party): Nora Sovira, Indonesia University

Tracking Information

• First Submitted Date: May 7, 2019
• First Posted Date: May 14, 2019
• Last Update Posted Date: May 14, 2019
• Actual Study Start Date: December 30, 2016
• Actual Primary Completion Date: July 30, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2019)

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

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: May 10, 2019)

• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major
• Official Title: The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell
• Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Beta thalassemia major children

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double masking. No any information about treatment or placebo in participant, investigator, care provider and outcome assessor

Primary Purpose: Treatment

Condition

• Beta Thalassemia Major Anemia
• Hemolysis
• Oxidative Stress

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.
  Other Name: Santa E
• Drug: Placebo oral tablet
  Other Name: Alpha-tocopherol placebo

Study Arms

• 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.

  Interventions:

  • Drug: Alpha-Tocopherol
  • Drug: Placebo oral tablet
• Placebo Comparator: Control
  Placebo is the drug with the same shape and color as the alpha-tocopherol supplementation.
  Interventions:

  • Drug: Alpha-Tocopherol
  • Drug: Placebo oral tablet

Publications *

• 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.
• Voskou S, Aslan M, Fanis P, Phylactides M, Kleanthous M. Oxidative stress in beta-thalassaemia and sickle cell disease. Redox Biol. 2015 Dec;6:226-239. doi: 10.1016/j.redox.2015.07.018. Epub 2015 Aug 1.
• 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.
• 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.
• Kormoczi GF, Saemann 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. doi: 10.1111/j.1365-2362.2006.01617.x.
• 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.
• 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. doi: 10.1002/ajh.20387.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 10, 2019): 40
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 1, 2017
• Actual Primary Completion Date: July 30, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Indonesia

Administrative Information

• NCT Number: NCT03948737
• Other Study ID Numbers: NSovira
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Nora Sovira, Indonesia University
• Original Responsible Party: Same as current
• Current Study Sponsor: Indonesia University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Pustika Amalia, Consultant; Hematology Oncologist Head Division of Child Health of Universitas Indonesia

• PRS Account: Indonesia University
• Verification Date: May 2019