The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major
Primary Purpose
Beta Thalassemia Major Anemia, Hemolysis, Oxidative Stress
Status
Completed
Phase
Not Applicable
Locations
Indonesia
Study Type
Interventional
Intervention
Alpha-Tocopherol
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Beta Thalassemia Major Anemia focused on measuring Haptoglobin, Hemopexin, Hemolysis, Malondialdehyde, Glutathione, Oxidative stress, Alpha-Tocopherol
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
Sites / Locations
- Thalassemia Centre Kiara RSUP Dr.CiptoMangunkusumo
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Alpha-Tocopgerol
Control
Arm Description
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 is the drug with the same shape and color as the alpha-tocopherol supplementation.
Outcomes
Primary Outcome Measures
The effects of α-tocopherol in hemolysis marker on the red cell membrane of β-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
Secondary Outcome Measures
The effects of α-tocopherol in oxidative stress marker on the red cell membrane of β-thalassemia major
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
The Glutathione as endogenous antioxidant marker on alpha-tocopherol treatment was assessed by ELISA method by using GT40 for Glutathione kit
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03948737
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
December 30, 2016 (Actual)
Primary Completion Date
July 30, 2017 (Actual)
Study Completion Date
August 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indonesia University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Beta Thalassemia Major Anemia, Hemolysis, Oxidative Stress
Keywords
Haptoglobin, Hemopexin, Hemolysis, Malondialdehyde, Glutathione, Oxidative stress, Alpha-Tocopherol
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Beta thalassemia major children
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double masking. No any information about treatment or placebo in participant, investigator, care provider and outcome assessor
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Alpha-Tocopgerol
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Placebo is the drug with the same shape and color as the alpha-tocopherol supplementation.
Intervention Type
Drug
Intervention Name(s)
Alpha-Tocopherol
Other Intervention Name(s)
Santa E
Intervention Description
all of the subjects in the alpha-tocopherol group received alpha-tocopherol orally, doses adjusted by age for 4 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
Alpha-tocopherol placebo
Primary Outcome Measure Information:
Title
The effects of α-tocopherol in hemolysis marker on the red cell membrane of β-thalassemia major
Description
The plasma haptoglobin and hemolysis as hemolysis marker on alpha-tocopherol treatment were assessed by ELISA using Haptoglobin and Hemopexin kit for human
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
The effects of α-tocopherol in oxidative stress marker on the red cell membrane of β-thalassemia major
Description
The malondialdehyde plasma level as oxidative stress marker on alpha-tocopherol treatment was assessed by Spectrophotometry using TBARS method.
Time Frame
4 weeks
Title
The effects of α-tocopherol in endogenous antioxidant on the red cell membrane of β-thalassemia major
Description
The Glutathione as endogenous antioxidant marker on alpha-tocopherol treatment was assessed by ELISA method by using GT40 for Glutathione kit
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pustika Amalia, Consultant
Organizational Affiliation
Hematology Oncologist Head Division of Child Health of Universitas Indonesia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thalassemia Centre Kiara RSUP Dr.CiptoMangunkusumo
City
Jakarta Pusat
State/Province
Jakarta
ZIP/Postal Code
10340
Country
Indonesia
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29333256
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.
Results Reference
result
PubMed Identifier
26285072
Citation
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.
Results Reference
result
PubMed Identifier
26175690
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.
Results Reference
result
PubMed Identifier
23995229
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: 10.1038/cdd.2013.113. Epub 2013 Aug 30.
Results Reference
result
PubMed Identifier
16506966
Citation
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.
Results Reference
result
PubMed Identifier
25389409
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.
Results Reference
result
PubMed Identifier
15981230
Citation
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.
Results Reference
result
PubMed Identifier
23105782
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.
Results Reference
result
Links:
URL
https://druginfo.nlm.nih.gov/drugportal/name/alpha-Tocopherol+succinate
Description
Drug information of alpha-Tocopherol
Learn more about this trial
The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major
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