EKLF Mutations in Beta Thalassemia PatientsNCT06433570
Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients
An observational study of EKLF Mutations in Beta Thalassemia Patients, run by Assiut University.
Trial summary
Detection of KLF1 gene mutations in patients with beta thalassemia considering the alpha and beta molecular status of these patients. Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- EKLF Mutations in Beta Thalassemia Patients
- What is being tested?
- multiplex PCR
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Jun 2024to Dec 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 Any age
- All sexes
- Child, Adult, Older adult
Study population: cross sectional study
Who may be able to join
- Patients with β-thalassemia (intermedia and major) of both genders at any age
Who cannot join
- Patients with any other type of haemolytic anaemias.
- Patients on Hydroxyurea therapy
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
- Detection of KLF1 gene mutations in patients with beta thalassemia considering the alpha and beta molecular status of these patients.
- Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia.
Read the detailed description
Thalassemias are inherited abnormalities in globin chain synthesis of hemoglobin and one of the most common single gene disorders in the world.
β-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of haemoglobin. Three clinical and hematological conditions of increasing severity are recognized: the β-thalassemia trait, thalassemia intermedia and thalassemia major.
The Erythroid Kruppel-like factor (EKLF or KLF1) is a master regulator of terminal erythroid differentiation, controlling expression of many key pathways and structures including cell division, the cell membrane and cytoskeleton, heme and globin synthesis.
The KLF1 works as a key regulator of γ-globin to β-globin switch by up-regulation of PUM1 that binds to fetal γ globin mRNA impairing its stability and translation and by Bcl11a expression that represses γ-globin expression.
Previous studies reported that KLF1 mutations have been identified in a variety of erythroid conditions like hereditary persistence of fetal hemoglobin, Congenital dyserythropoietic anemia and borderline HbA2.
An Indian study on KLF1 gene variations found a marginal significance in the thalassemia intermedia group (14%) as against the thalassemia major group (2.0%).
Also, a case report on a Chinese family with twin brothers, both of whom had the same genotype of β0/β0, reported that KLF1 mutations have a role in modulating the phenotypic severity of β-thalassemia.
In our study, where there is high incidence of beta thalassemia in Egypt, we try to detect KLF1 mutations and its relation to clinical phenotype of these patients.
- Being tested
- multiplex PCR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
multiplex PCRGenetic
Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients using multiplex PCR
| Study group | Role | What they receive |
|---|---|---|
| 50 patients with beta thalassemia intermedia | Not described Receives: Genetic: multiplex PCR | |
| 50 patients with beta thalassemia major | Not described Receives: Genetic: multiplex PCR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection of KLF1 gene mutations in patients with beta thalassemia considering the beta molecular status of these patients
Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia and with the clinical data (frequency of blood transfusions).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2024
- Study startJun 2024 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for EKLF Mutations in Beta Thalassemia PatientsStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Abd Elnasser Mahmoud, Assiut University
- Investigators
- Reem Abd Elkhalek Mohamed, lecturer, Study director, Assiut UniversityHebatallah Ahmed, lecturer, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06433570
- Sponsor's protocol ID
- EKLFmutation in β thalassemia
- Status last verified
- May 2024
- First submitted
- 23 May 2024
- Last updated
- 29 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Siatecka M, Bieker JJ. The multifunctional role of EKLF/KLF1 during erythropoiesis. Blood. 2011 Aug 25;118(8):2044-54. doi: 10.1182/blood-2011-03-331371. Epub 2011 May 25.
PubMed 21613252Tallack MR, Perkins AC. Three fingers on the switch: Kruppel-like factor 1 regulation of gamma-globin to beta-globin gene switching. Curr Opin Hematol. 2013 May;20(3):193-200. doi: 10.1097/MOH.0b013e32835f59ba.
PubMed 23474875Elagooz 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 35667093Borg 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 20676099Srivorakun H, Thawinan W, Fucharoen G, Sanchaisuriya K, Fucharoen S. Thalassemia and erythroid transcription factor KLF1 mutations associated with borderline hemoglobin A2 in the Thai population. Arch Med Sci. 2020 Aug 11;18(1):112-120. doi: 10.5114/aoms.2020.93392. eCollection 2022.
PubMed 35154532Waye JS, Eng B. Kruppel-like factor 1: hematologic phenotypes associated with KLF1 gene mutations. Int J Lab Hematol. 2015 May;37 Suppl 1:78-84. doi: 10.1111/ijlh.12356.
PubMed 25976964Hariharan P, Colah R, Ghosh K, Nadkarni A. Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders. Genomics. 2019 Dec;111(6):1771-1776. doi: 10.1016/j.ygeno.2018.11.032. Epub 2018 Dec 5.
PubMed 30529538Xie XM, Liu YN, Li J, Jiang F, Li DZ. A Kruppel-Like Factor 1 Gene Mutation Ameliorates the Severity of beta-Thalassemia: A Case Report. Hemoglobin. 2019 Mar;43(2):137-139. doi: 10.1080/03630269.2019.1607373. Epub 2019 May 21.
PubMed 31111750El-Beshlawy A, Youssry I. Prevention of hemoglobinopathies in Egypt. Hemoglobin. 2009;33 Suppl 1:S14-20. doi: 10.3109/03630260903346395.
PubMed 20001619Origa R. beta-Thalassemia. Genet Med. 2017 Jun;19(6):609-619. doi: 10.1038/gim.2016.173. Epub 2016 Nov 3.
PubMed 27811859
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients
- ClinicalTrials.gov ID
- NCT06433570
- Acronym / sponsor ID
- EKLFmutation in β thalassemia
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Jun 2024 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 29 May 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.
- Detection of KLF1 gene mutations in patients with beta thalassemia considering the alpha and beta molecular status of these patients.
- Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia.
Detailed description
Thalassemias are inherited abnormalities in globin chain synthesis of hemoglobin and one of the most common single gene disorders in the world.
β-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of haemoglobin. Three clinical and hematological conditions of increasing severity are recognized: the β-thalassemia trait, thalassemia intermedia and thalassemia major.
The Erythroid Kruppel-like factor (EKLF or KLF1) is a master regulator of terminal erythroid differentiation, controlling expression of many key pathways and structures including cell division, the cell membrane and cytoskeleton, heme and globin synthesis.
The KLF1 works as a key regulator of γ-globin to β-globin switch by up-regulation of PUM1 that binds to fetal γ globin mRNA impairing its stability and translation and by Bcl11a expression that represses γ-globin expression.
Previous studies reported that KLF1 mutations have been identified in a variety of erythroid conditions like hereditary persistence of fetal hemoglobin, Congenital dyserythropoietic anemia and borderline HbA2.
An Indian study on KLF1 gene variations found a marginal significance in the thalassemia intermedia group (14%) as against the thalassemia major group (2.0%).
Also, a case report on a Chinese family with twin brothers, both of whom had the same genotype of β0/β0, reported that KLF1 mutations have a role in modulating the phenotypic severity of β-thalassemia.
In our study, where there is high incidence of beta thalassemia in Egypt, we try to detect KLF1 mutations and its relation to clinical phenotype of these patients.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 50 patients with beta thalassemia intermedia | – | Genetic: multiplex PCR |
| 50 patients with beta thalassemia major | – | Genetic: multiplex PCR |
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- cross sectional study
Key inclusion criteria (1 listed)
- Patients with β-thalassemia (intermedia and major) of both genders at any age
Key exclusion criteria (2 listed)
- Patients with any other type of haemolytic anaemias.
- Patients on Hydroxyurea therapy
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 |
|---|---|---|
| multiplex PCRDetection of Krupple Like Factor -1(KLF1/ EKLF) DNA Mutations in Beta Thalassemia Patients using multiplex PCR | Genetic | 50 patients with beta thalassemia intermedia, 50 patients with beta thalassemia major |
Primary outcome
Detection of KLF1 gene mutations in patients with beta thalassemia considering the beta molecular status of these patients
Time frame: Baseline
Study the relation between genotypic mutational status of KLF1 mutation with the level of Hb F and Hb A2 in the patients of beta thalassemia and with the clinical data (frequency of blood transfusions).
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 29 May 2024.
- Background: PubMed 21613252Siatecka M, Bieker JJ. The multifunctional role of EKLF/KLF1 during erythropoiesis. Blood. 2011 Aug 25;118(8):2044-54. doi: 10.1182/blood-2011-03-331371. Epub 2011 May 25.
- Background: PubMed 23474875Tallack MR, Perkins AC. Three fingers on the switch: Kruppel-like factor 1 regulation of gamma-globin to beta-globin gene switching. Curr Opin Hematol. 2013 May;20(3):193-200. doi: 10.1097/MOH.0b013e32835f59ba.
- 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 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 35154532Srivorakun H, Thawinan W, Fucharoen G, Sanchaisuriya K, Fucharoen S. Thalassemia and erythroid transcription factor KLF1 mutations associated with borderline hemoglobin A2 in the Thai population. Arch Med Sci. 2020 Aug 11;18(1):112-120. doi: 10.5114/aoms.2020.93392. eCollection 2022.
- Background: PubMed 25976964Waye JS, Eng B. Kruppel-like factor 1: hematologic phenotypes associated with KLF1 gene mutations. Int J Lab Hematol. 2015 May;37 Suppl 1:78-84. doi: 10.1111/ijlh.12356.
- Background: PubMed 30529538Hariharan P, Colah R, Ghosh K, Nadkarni A. Differential role of Kruppel like factor 1 (KLF1) gene in red blood cell disorders. Genomics. 2019 Dec;111(6):1771-1776. doi: 10.1016/j.ygeno.2018.11.032. Epub 2018 Dec 5.
- Background: PubMed 31111750Xie XM, Liu YN, Li J, Jiang F, Li DZ. A Kruppel-Like Factor 1 Gene Mutation Ameliorates the Severity of beta-Thalassemia: A Case Report. Hemoglobin. 2019 Mar;43(2):137-139. doi: 10.1080/03630269.2019.1607373. Epub 2019 May 21.
- Background: PubMed 20001619El-Beshlawy A, Youssry I. Prevention of hemoglobinopathies in Egypt. Hemoglobin. 2009;33 Suppl 1:S14-20. doi: 10.3109/03630260903346395.
- Results publication: PubMed 27811859Origa R. beta-Thalassemia. Genet Med. 2017 Jun;19(6):609-619. doi: 10.1038/gim.2016.173. Epub 2016 Nov 3.
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.
Reem Abd Elkhalek Mohamed, lecturer study director
Assiut University
Hebatallah Ahmed, lecturer study director
Assiut University
Questions about this trial
What is this clinical trial studying?
An observational study of EKLF Mutations in Beta Thalassemia Patients, run by Assiut University.
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 1 inclusion and 2 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 29 May 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 mohamed mahmoud (01113225644, doctor4egypt2011@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection of KLF1 gene mutations in patients with beta thalassemia considering the beta molecular status of these patients (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 NCT06433570, which also lists 10 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 29 May 2024.