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出境医 / 临床实验 / The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major

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

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.

Condition or disease Intervention/treatment Phase
Beta Thalassemia Major Anemia Hemolysis Oxidative Stress Drug: Alpha-Tocopherol Drug: Placebo oral tablet Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
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
Official Title: The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell
Actual Study Start Date : December 30, 2016
Actual Primary Completion Date : July 30, 2017
Actual Study Completion Date : August 1, 2017
Arms and Interventions
Arm Intervention/treatment
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.

 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
Placebo Comparator: Control
Placebo is the drug with the same shape and color as the alpha-tocopherol supplementation.
 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
Outcome Measures
Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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


Eligibility Criteria
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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
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Indonesia
Thalassemia Centre Kiara RSUP Dr.CiptoMangunkusumo
Jakarta Pusat, Jakarta, Indonesia, 10340
Sponsors and Collaborators
Indonesia University
Investigators
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Principal Investigator: Pustika Amalia, Consultant Hematology Oncologist Head Division of Child Health of Universitas Indonesia
Tracking Information
First Submitted Date  ICMJE May 7, 2019
First Posted Date  ICMJE May 14, 2019
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE December 30, 2016
Actual Primary Completion Date July 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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  ICMJE
  • Beta Thalassemia Major Anemia
  • Hemolysis
  • Oxidative Stress
Intervention  ICMJE
  • 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  ICMJE
  • 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. 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2019) 		40
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 1, 2017
Actual Primary Completion Date July 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Indonesia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03948737
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Nora Sovira, Indonesia University
Study Sponsor  ICMJE Indonesia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pustika Amalia, Consultant Hematology Oncologist Head Division of Child Health of Universitas Indonesia
PRS Account Indonesia University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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