Beta Thalassemia Major AnemiaNCT03948737
The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell Membrane Beta-thalassemia Major
A study testing Alpha-Tocopherol in people with Beta Thalassemia Major Anemia and Hemolysis, run by Universitas Indonesia at 1 site in Indonesia.
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. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Beta Thalassemia Major Anemia, Hemolysis, Oxidative Stress
- What is being tested?
- Alpha-Tocopherol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteIndonesia
- Study dates
- 30 Dec 2016to 1 Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- received frequent transfusions,
- iron chelation
- aged 5 - 18-year-olds
- with no other hematologic disorders
- does not consume any other antioxidants or herbal supplements
Who cannot join
- the acute or chronic infection including hepatitis B or hepatitis C,
- splenectomy
- liver failure
- abnormality level of lipid test
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
Thalassemia Centre Kiara RSUP Dr.CiptoMangunkusumo
Jakarta Pusat, Jakarta Special Capital Region, 10340
About this study
Official title: The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell
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.
Read the 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.
- Conditions
- Beta Thalassemia Major Anemia, Hemolysis, Oxidative Stress
- Being tested
- Alpha-Tocopherol, Placebo oral tablet
- Keywords
- Haptoglobin, Hemopexin, Hemolysis, Malondialdehyde, Glutathione, Oxidative stress, Alpha-Tocopherol
- Medical subject headings
- Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-TocopherolDrug
Also called Santa E
all of the subjects in the alpha-tocopherol group received alpha-tocopherol orally, doses adjusted by age for 4 weeks of treatment.
Placebo oral tabletDrug
Also called Alpha-tocopherol placebo
| Study group | Role | What they receive |
|---|---|---|
| Alpha-Tocopgerol | Active comparator | 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. Receives: Drug: Alpha-Tocopherol; Drug: Placebo oral tablet |
| Control | Placebo comparator | Placebo is the drug with the same shape and color as the alpha-tocopherol supplementation. Receives: Drug: Alpha-Tocopherol; Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 4 weeks
Secondary outcomes (2)
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.
Measured: 4 weeks
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
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start30 Dec 2016
- Primary completion30 Jul 2017
- Study completion1 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Beta Thalassemia Major AnemiaStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Beta thalassemia major children
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nora Sovira, Universitas Indonesia
- Investigators
- Pustika Amalia, Consultant, Principal investigator, Hematology Oncologist Head Division of Child Health of Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03948737
- Sponsor's protocol ID
- NSovira
- Status last verified
- May 2019
- First submitted
- 7 May 2019
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29333256Voskou 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.
PubMed 26285072Smith 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.
PubMed 26175690Schaer 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.
PubMed 23995229Kormoczi 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.
PubMed 16506966Schaer 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.
PubMed 25389409Chow 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.
PubMed 15981230Ghone 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.
PubMed 23105782
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell
- ClinicalTrials.gov ID
- NCT03948737
- Acronym / sponsor ID
- NSovira
- Conditions
- Beta Thalassemia Major Anemia, Hemolysis, Oxidative Stress
- Keywords
- Haptoglobin, Hemopexin, Hemolysis, Malondialdehyde, Glutathione, Oxidative stress, Alpha-Tocopherol
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Study start
- 30 Dec 2016 (actual)
- Primary completion
- 30 Jul 2017 (actual)
- Study completion
- 1 Aug 2017 (actual)
- First posted
- 14 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Beta thalassemia major children
| Arm | Type | Receives |
|---|---|---|
| Alpha-Tocopgerol | Active comparator | Drug: Alpha-Tocopherol, Drug: Placebo oral tabletAlpha-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. |
| Control | Placebo comparator | Drug: Alpha-Tocopherol, Drug: Placebo oral tabletPlacebo is the drug with the same shape and color as the alpha-tocopherol supplementation. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- received frequent transfusions,
- iron chelation
- aged 5 - 18-year-olds
- with no other hematologic disorders
- does not consume any other antioxidants or herbal supplements
Key exclusion criteria (4 listed)
- the acute or chronic infection including hepatitis B or hepatitis C,
- splenectomy
- liver failure
- abnormality level of lipid test
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alpha-TocopherolAlso: Santa Eall of the subjects in the alpha-tocopherol group received alpha-tocopherol orally, doses adjusted by age for 4 weeks of treatment. | Drug | Alpha-Tocopgerol, Control |
| Placebo oral tabletAlso: Alpha-tocopherol placebo | Drug | Alpha-Tocopgerol, Control |
Primary outcome
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
2 secondary outcomes
The effects of α-tocopherol in oxidative stress marker on the red cell membrane of β-thalassemia major
Time frame: 4 weeks
The effects of α-tocopherol in endogenous antioxidant on the red cell membrane of β-thalassemia major
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- Results publication: PubMed 29333256Fibach 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 publication: PubMed 26285072Voskou 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 publication: PubMed 26175690Smith 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 publication: PubMed 23995229Schaer 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 publication: PubMed 16506966Kormoczi 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 publication: PubMed 25389409Schaer 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 publication: PubMed 15981230Chow 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 publication: PubMed 23105782Ghone 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.
- Drug information of alpha-TocopherolLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pustika Amalia, Consultant principal investigator
Hematology Oncologist Head Division of Child Health of Universitas Indonesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alpha-Tocopherol in people with Beta Thalassemia Major Anemia and Hemolysis, run by Universitas Indonesia at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The effects of α-tocopherol in hemolysis marker on the red cell membrane of β-thalassemia major (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03948737, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.