β-thalassemiaNCT06440603
EKLF Gene Expression in β-thalassemia
An observational study of β-thalassemia, run by Rofaida Hassan Ahmed.
Trial summary
1. Studying the effect of expression pattern of EKLF gene in β-thalassemic patients. 2. Detecting the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients. Read more about this study
- Who is it for?
- Ages 5 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- β-thalassemia
- What is being tested?
- PCR
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2024to 1 Jul 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Patients > 5 years diagnosed with β-thalassemia including both thalassemia major and intermedia
Who may be able to join
- patients with β-thalassemia (major and intermedia).
- patients are of both sexes (male or female) at any age
Who cannot join
- patients with any other types of hemolytic anaemia
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Erythroid Krüppel Like Factor (EKLF) Gene Expression in β-thalassemia Patients
- Studying the effect of expression pattern of EKLF gene in β-thalassemic patients.
- Detecting the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Read the detailed description
β-thalassemia is a common inherited disorder caused by absent or reduced synthesis of the hemoglobin subunit beta (beta globin chain) , it has 3 clinical types; minor which is a carrier state, intermedia and major which are differentiated by blood transfusion dependency and lab findings.
In β-thalassemia, insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors, impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells. As a result, a significant anaemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs.
These mutations are primarily point mutations that affect transcriptional control, translation, and splicing of the beta haemoglobin gene and gene expression.
The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean, the Middle East, and Southeast and Central Asia. Approximately 68000 children are born with beta-thalassemia. Its prevalence is 80-90 million carriers, around 1.5% of the global population.
Erythroid Krüppel-like factor (EKLF or KLF1) is a transcriptional regulator that plays a major role in lineage-restricted control of gene expression. KLF1 expression and activity are tightly controlled in a temporal and differentiation stage-specific manner. The mechanisms by which KLF1 is regulated encompass a range of biological processes, including control of KLF1 RNA transcription, protein stability, localization, and posttranslational modifications. Intact KLF1 regulation is essential to correctly regulate erythroid function by gene transcription and to maintain hematopoietic lineage homeostasis by ensuring a proper balance of erythroid/megakaryocytic differentiation. In turn, KLF1 regulates erythroid biology by a wide variety of mechanisms, including gene activation and repression by regulation of chromatin configuration, transcriptional initiation and elongation, and localization of gene loci to transcription factories in the nucleus.
Previous studies have shown that EKLF plays a critical role in regulating the developmental switch between fetal and adult haemoglobin expression, both by direct activation of β-globin and indirect repression of γ-globin gene expression in adult erythroid progenitors via regulation of Bcl11a and ZBTB7a and PUM1.
PUM1 is a direct posttranscriptional regulator of β-globin switching, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin (HBG1) mRNA stability and translational efficiency, which culminates in reduced γ-globin protein levels.
So, EKLF is too important in erythropoiesis and Hb switching that there are clinical trials nowadays depending on the molecules that targeted by EKLF (eg:Bcl11a, ZBTB7a and PUM1) and their role in Hb switching in treatment of thalassemia and other haemolytic anaemias as sickle cell anaemia.
- Conditions
- β-thalassemia
- Being tested
- PCR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCRDiagnostic test
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detection of EKLF:
- The method of total RNA extraction: TRIZOL and TRIZOL LS.
- The purity and concentration of the RNA will be measured using Nano Drop 2000 instument.
- cDNA will be done with primers using thr Goscript Reverse Transcription System
| Study group | Role | What they receive |
|---|---|---|
| Group I | Age and sex matched healthy Control Receives: Diagnostic Test: PCR | |
| Group 2 | 50 patients with β-thalassemia major Receives: Diagnostic Test: PCR | |
| Group 3 | 50 patients with β-thalassemia intermedia Receives: Diagnostic Test: PCR |
What is being measured
The primary outcome is the main question the study is designed to answer.
study the expression pattern of EKLF gene in β-thalassemic patients, work by measuring mRNA levels
study the expression pattern of EKLF gene by Real-time polymerase chain reaction (RT-qPCR) in β-thalassemic patients
Measured: Baseline
Secondary outcomes (1)
study the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
study the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start1 Jul 2024 (estimated)
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for β-thalassemiaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rofaida Hassan Ahmed
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rofaida Hassan Ahmed, Assiut University
- Investigators
- Eman Naser Eldin, Study director, Assiut UniversitySherif Helmy, Study director, Assiut UniversityReem Elagoz, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06440603
- Sponsor's protocol ID
- β-thalassemia
- Status last verified
- May 2024
- First submitted
- 19 May 2024
- Last updated
- 4 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a011643. doi: 10.1101/cshperspect.a011643.
PubMed 23209159Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010 Feb;12(2):61-76. doi: 10.1097/GIM.0b013e3181cd68ed.
PubMed 20098328Origa R. beta-Thalassemia. Genet Med. 2017 Jun;19(6):609-619. doi: 10.1038/gim.2016.173. Epub 2016 Nov 3.
PubMed 27811859Yien YY, Bieker JJ. EKLF/KLF1, a tissue-restricted integrator of transcriptional control, chromatin remodeling, and lineage determination. Mol Cell Biol. 2013 Jan;33(1):4-13. doi: 10.1128/MCB.01058-12. Epub 2012 Oct 22.
PubMed 23090966Borg J, Papadopoulos P, Georgitsi M, Gutierrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgur Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet. 2010 Sep;42(9):801-5. doi: 10.1038/ng.630. Epub 2010 Aug 1.
PubMed 20676099Elagooz R, Dhara AR, Gott RM, Adams SE, White RA, Ghosh A, Ganguly S, Man Y, Owusu-Ansah A, Mian OY, Gurkan UA, Komar AA, Ramamoorthy M, Gnanapragasam MN. PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin. Blood Adv. 2022 Dec 13;6(23):6016-6022. doi: 10.1182/bloodadvances.2021006730.
PubMed 35667093Siatecka M, Soni S, Planutis A, Bieker JJ. Transcriptional activity of erythroid Kruppel-like factor (EKLF/KLF1) modulated by PIAS3 (protein inhibitor of activated STAT3). J Biol Chem. 2015 Apr 10;290(15):9929-40. doi: 10.1074/jbc.M114.610246. Epub 2015 Feb 24.
PubMed 25713074
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythroid Krüppel Like Factor (EKLF) Gene Expression in β-thalassemia Patients
- ClinicalTrials.gov ID
- NCT06440603
- Acronym / sponsor ID
- β-thalassemia
- Conditions
- β-thalassemia
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Rofaida Hassan AhmedUniversity, hospital or other
- Study start
- 1 Jul 2024 (estimated)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 4 Jun 2024 (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.
- Studying the effect of expression pattern of EKLF gene in β-thalassemic patients.
- Detecting the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Detailed description
β-thalassemia is a common inherited disorder caused by absent or reduced synthesis of the hemoglobin subunit beta (beta globin chain) , it has 3 clinical types; minor which is a carrier state, intermedia and major which are differentiated by blood transfusion dependency and lab findings.
In β-thalassemia, insufficient production of the β-globin molecule results in an excess of free α-globin chains that can precipitate within erythroid precursors, impairing their maturation and leads to death of these precursors and ineffective production of erythroid cells. As a result, a significant anaemia occurs and the consequent expansion of erythroid precursors can lead to secondary problems in bones and other organs.
These mutations are primarily point mutations that affect transcriptional control, translation, and splicing of the beta haemoglobin gene and gene expression.
The frequency of beta-thalassemia mutations varies by regions of the world with the highest prevalence in the Mediterranean, the Middle East, and Southeast and Central Asia. Approximately 68000 children are born with beta-thalassemia. Its prevalence is 80-90 million carriers, around 1.5% of the global population.
Erythroid Krüppel-like factor (EKLF or KLF1) is a transcriptional regulator that plays a major role in lineage-restricted control of gene expression. KLF1 expression and activity are tightly controlled in a temporal and differentiation stage-specific manner. The mechanisms by which KLF1 is regulated encompass a range of biological processes, including control of KLF1 RNA transcription, protein stability, localization, and posttranslational modifications. Intact KLF1 regulation is essential to correctly regulate erythroid function by gene transcription and to maintain hematopoietic lineage homeostasis by ensuring a proper balance of erythroid/megakaryocytic differentiation. In turn, KLF1 regulates erythroid biology by a wide variety of mechanisms, including gene activation and repression by regulation of chromatin configuration, transcriptional initiation and elongation, and localization of gene loci to transcription factories in the nucleus.
Previous studies have shown that EKLF plays a critical role in regulating the developmental switch between fetal and adult haemoglobin expression, both by direct activation of β-globin and indirect repression of γ-globin gene expression in adult erythroid progenitors via regulation of Bcl11a and ZBTB7a and PUM1.
PUM1 is a direct posttranscriptional regulator of β-globin switching, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin (HBG1) mRNA stability and translational efficiency, which culminates in reduced γ-globin protein levels.
So, EKLF is too important in erythropoiesis and Hb switching that there are clinical trials nowadays depending on the molecules that targeted by EKLF (eg:Bcl11a, ZBTB7a and PUM1) and their role in Hb switching in treatment of thalassemia and other haemolytic anaemias as sickle cell anaemia.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group I | – | Diagnostic Test: PCRAge and sex matched healthy Control |
| Group 2 | – | Diagnostic Test: PCR50 patients with β-thalassemia major |
| Group 3 | – | Diagnostic Test: PCR50 patients with β-thalassemia intermedia |
Who may qualify
- Ages
- 5 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients > 5 years diagnosed with β-thalassemia including both thalassemia major and intermedia
Key inclusion criteria (2 listed)
- patients with β-thalassemia (major and intermedia).
- patients are of both sexes (male or female) at any age
Key exclusion criteria (1 listed)
- patients with any other types of hemolytic anaemia
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 |
|---|---|---|
| PCRReverse transcription-quantitative polymerase chain reaction (RT-qPCR) for detection of EKLF: * The method of total RNA extraction: TRIZOL and TRIZOL LS. * The purity and concentration of the RNA will be measured using Nano Drop 2000 instument. * cDNA will be done with primers using thr Goscript Reverse Transcription System | Diagnostic test | Group 2, Group 3, Group I |
Primary outcome
study the expression pattern of EKLF gene in β-thalassemic patients, work by measuring mRNA levels
Time frame: Baseline
study the expression pattern of EKLF gene by Real-time polymerase chain reaction (RT-qPCR) in β-thalassemic patients
1 secondary outcome
study the correlation between the gene expression of EKLF and the clinical phenotype of β-thalassemic patients.
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Background: PubMed 23209159Sankaran VG, Orkin SH. The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013 Jan 1;3(1):a011643. doi: 10.1101/cshperspect.a011643.
- Background: PubMed 20098328Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010 Feb;12(2):61-76. doi: 10.1097/GIM.0b013e3181cd68ed.
- Background: PubMed 27811859Origa R. beta-Thalassemia. Genet Med. 2017 Jun;19(6):609-619. doi: 10.1038/gim.2016.173. Epub 2016 Nov 3.
- Background: PubMed 23090966Yien YY, Bieker JJ. EKLF/KLF1, a tissue-restricted integrator of transcriptional control, chromatin remodeling, and lineage determination. Mol Cell Biol. 2013 Jan;33(1):4-13. doi: 10.1128/MCB.01058-12. Epub 2012 Oct 22.
- Background: PubMed 20676099Borg J, Papadopoulos P, Georgitsi M, Gutierrez L, Grech G, Fanis P, Phylactides M, Verkerk AJ, van der Spek PJ, Scerri CA, Cassar W, Galdies R, van Ijcken W, Ozgur Z, Gillemans N, Hou J, Bugeja M, Grosveld FG, von Lindern M, Felice AE, Patrinos GP, Philipsen S. Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet. 2010 Sep;42(9):801-5. doi: 10.1038/ng.630. Epub 2010 Aug 1.
- Background: PubMed 35667093Elagooz R, Dhara AR, Gott RM, Adams SE, White RA, Ghosh A, Ganguly S, Man Y, Owusu-Ansah A, Mian OY, Gurkan UA, Komar AA, Ramamoorthy M, Gnanapragasam MN. PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin. Blood Adv. 2022 Dec 13;6(23):6016-6022. doi: 10.1182/bloodadvances.2021006730.
- Background: PubMed 25713074Siatecka M, Soni S, Planutis A, Bieker JJ. Transcriptional activity of erythroid Kruppel-like factor (EKLF/KLF1) modulated by PIAS3 (protein inhibitor of activated STAT3). J Biol Chem. 2015 Apr 10;290(15):9929-40. doi: 10.1074/jbc.M114.610246. Epub 2015 Feb 24.
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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.
Eman Naser Eldin study director
Assiut University
Sherif Helmy study director
Assiut University
Reem Elagoz study director
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of β-thalassemia, run by Rofaida Hassan Ahmed.
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 2 inclusion and 1 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: opening soon, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rofida Hassan (+2 1019935111, mahaseb_rofaida@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
study the expression pattern of EKLF gene in β-thalassemic patients, work by measuring mRNA levels (time frame: Baseline). 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 NCT06440603, which also lists 7 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 4 Jun 2024.