Sickle Cell DiseaseINHERENTNCT05799118
Study of the Role of Genetic Modifiers in Hemoglobinopathies
An observational study of Sickle Cell Disease and Thalassemia, Beta, run by Cyprus Institute of Neurology and Genetics at 26 sites in 16 countries.
Trial summary
This study will investigate the role of genetic modifiers in hemoglobinopathies through a large-scale, multi-ethnic genome-wide association study (GWAS). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Sickle Cell Disease, Thalassemia, Beta, Thalassemia Alpha
- What is being tested?
- GWAS
- How many people
- 30,000 participants
- Where
- 26 sitesin 16 countries
- Study dates
- 1 Oct 2022to 30 Sep 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals diagnosed with an inherited hemoglobinopathy and are under regular follow-up in the participating centers
Who may be able to join
- Clinical diagnosis of an inherited hemoglobinopathy, including sickle cell disease (SCD), β-thalassemia, and α-thalassemia; all genotypes will be considered.
- Age ≥ 2 years old at the time of the collection of the phenotypic data.
- There will be no limits on study participants in terms of gender, ethnicity, morbidities.
Who cannot join
- Patients treated with stem cell transplantation or genetic therapy.
- Age < 2 years old at the time of the collection of the phenotypic data.
- Patient or legal representative for minors unwilling or unable to give consent.
Trial locations and contacts
26 sites in 16 countries. Contact the study team or a site near you to ask about taking part.
26 sites in 16 countries
Cyprus4 sites, 4 recruiting
- Recruiting
Larnaca General Hospital
Larnaca
Maria Sitarou, MD
- Recruiting
Limassol General Hospital
Limassol
Michael Hadjigavriel, MD
- Recruiting
Archbishop Makarios III Hospital
Nicosia
Soteroula Christou, MD
- Recruiting
Paphos General Hospital
Paphos
Thomas Dimitriou, MD
Greece4 sites, 4 recruiting
- Recruiting
Hippokrateio Hospital of Athens
Athens
Sophia Delicou, MD
- Recruiting
Laiko General Hospital
Athens
Maria Dimopoulou, MD
- Not yet recruiting
National and Kapodistrian University of Athens
Athens
Joanne Traeger-Synodinos, PhD
- Recruiting
General Hospital of Larissa
Larissa
Michael Diamantidis, MD
Malaysia3 sites, 3 recruiting
- Recruiting
Ampang Hospital
Ampang
Veena Selvaratnam, MD
- Recruiting
Universiti Kebangsaan Malaysia
Bangi
Raja Zahratul Azma, MD
- Recruiting
Universiti Sains Malaysia
Kota Bharu
Bin Alwi Zilfalil, MD, PhD
Nigeria3 sites, 3 recruiting
- Recruiting
University of Abuja
Abuja
Obiageli E Nnodu, MD
- Recruiting
Kaduna State University
Kaduna
Livingstone Dogara, MD
- Recruiting
Ahmadu Bello University
Zaria
Aliyu Waziri, MD
United States1 site, 1 recruiting
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Natasha Archer, MD
Angola1 site, 1 recruiting
- Recruiting
Lucrecia Paím Maternity
Luanda
Ligia Alves
Argentina1 site, 1 recruiting
- Not yet recruiting
University of Buenos Aires
Buenos Aires
Karen Scheps, PhD
Belgium1 site, 1 recruiting
- Not yet recruiting
University Hospitals Leuven
Leuven
Veerle Labarque, MD, PhD
Brunei1 site, 1 recruiting
- Not yet recruiting
Universiti Brunei Darussalam
Brunei
Mas Rina Wati Abdul Hamid
Democratic Republic of the Congo1 site, 1 recruiting
- Recruiting
Centre Hospitalier Monkole
Kinshasa
Leon Tshilolo, MD
Denmark1 site, 1 recruiting
- Recruiting
Rigshospitalet
Copenhagen
Andreas Birkedal Glenthøj, MD
Israel1 site, 1 recruiting
- Not yet recruiting
Emek Medical Centre
Afula
Ariel Koren, MD
Italy1 site, 1 recruiting
- Not yet recruiting
University of Turin
Turin
Giorgia Mandrile, PhD
Pakistan1 site, 1 recruiting
- Not yet recruiting
University of Lahore
Lahore
Ahmed Bilal, PhD
Portugal1 site, 1 recruiting
- Not yet recruiting
Centro Hospitalar e Universitário de Coimbra
Coimbra
Celeste Bento, PhD
Spain1 site, 1 recruiting
- Not yet recruiting
Hospital Clínico San Carlos
Madrid
Paloma Ropero, PhD
About this study
This study will investigate the role of genetic modifiers in hemoglobinopathies through a large-scale, multi-ethnic genome-wide association study (GWAS).
Read the detailed description
Hemoglobinopathies, including sickle cell disease (SCD) and beta-thalassemia, are prevalent diseases with variable clinical manifestation and severity that are thought to be governed, in part, by genetic modifiers. Despite the identification and characterization of a few putative genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or risk-stratify patients reliably. Also, it is expected that many additional genetic variants exist that can modify disease and its severity. This large-scale genome-wide association study (GWAS) will utilize SNP chips to investigate the genetic profile of individuals with hemoglobinopathies, thereby addressing the challenges of previous studies related to small sample sizes and low statistical power, while promoting the participation of diverse populations worldwide. The study aims to i) discover new genetic modifiers of hemoglobinopathies, ii) validate previously reported genetic modifiers, iii) pool and analyze existing genomic data, iv) standardize phenotypic descriptions, v) develop a research resource of disease-specific data generated in INHERENT, including genomic, phenotypic, and functional data, and vi) develop risk scores that can be used for patient stratification.
The main endpoints include:
- Worldwide demography, including numbers of patients, main genotypes, and overall disease severity/burden in participating centres
- Genetic modifiers affecting clinical or laboratory phenotypes of hemoglobinopathies, including
- overall survival in SCD and/or thalassemia,
- stroke and/or decreased neurocognitive function in SCD and/or thalassemia,
- renal impairment in SCD and/or thalassemia,
- leg ulcers in SCD,
- priapism in SCD,
- mild or severe acute pain and/or chronic pain syndromes in SCD,
- pulmonary hypertension in SCD and/or thalassemia,
- hyperhemolysis in SCD and/or thalassemia,
- fetal hemoglobin levels,
- degree of ineffective erythropoiesis,
- hepatic fibrosis/cirrhosis and/or cardiac siderosis,
- Genetic modifiers affecting response to treatment, including
- response to hydroxyurea,
- response to iron chelation treatment,
- response to emerging therapeutic agents
- Being tested
- GWAS
- Keywords
- GWAS, thalassemia, sickle cell disease, genetic modifiers
- Medical subject headings
- Anemia, Sickle Cell, beta-Thalassemia, alpha-Thalassemia, Hemoglobinopathies, Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GWASGenetic
The study will perform a GWAS experiments for all recruited subjects. The blood sample will be collected during routine clinical visits, only if DNA is not already available in existing biobanks. All individuals will provide consent for participation in the study.
| Study group | Role | What they receive |
|---|---|---|
| Cohort | Individuals with hemoglobinopathies Receives: Genetic: GWAS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic modifiers in haemoglobinopathies through GWAS
Number of genetic variants (SNPs) associated with disease-specific phenotypes
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2023
- Study start1 Oct 2022
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cyprus Institute of Neurology and Genetics
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Petros Kountouris, PhD, Cyprus Institute of Neurology and Genetics
- Investigators
- Petros Kountouris, PhD, Principal investigator, Cyprus Institute of Neurology and Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05799118
- Sponsor's protocol ID
- 1
- Acronym
- INHERENT
- Status last verified
- Mar 2024
- First submitted
- 10 Mar 2023
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kountouris P, Stephanou C, Archer N, Bonifazi F, Giannuzzi V, Kuo KHM, Maggio A, Makani J, Manu-Pereira MDM, Michailidou K, Nkya S, Nnodu OE, Trompeter S, Tshilolo L, Wonkam A, Zilfalil BA, Inusa BPD, Kleanthous M; on behalf of the International Hemoglobinopathy Research Network (INHERENT). The International Hemoglobinopathy Research Network (INHERENT): An international initiative to study the role of genetic modifiers in hemoglobinopathies. Am J Hematol. 2021 Nov 1;96(11):E416-E420. doi: 10.1002/ajh.26323. Epub 2021 Aug 30. No abstract available.
PubMed 34406671
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Role of Genetic Modifiers in Hemoglobinopathies
- ClinicalTrials.gov ID
- NCT05799118
- Acronym / sponsor ID
- INHERENT / 1
- Keywords
- GWAS, thalassemia, sickle cell disease, genetic modifiers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 30,000 participants (estimated)
- Lead sponsor
- Cyprus Institute of Neurology and GeneticsUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 5 Apr 2023 (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.
This study will investigate the role of genetic modifiers in hemoglobinopathies through a large-scale, multi-ethnic genome-wide association study (GWAS).
Detailed description
Hemoglobinopathies, including sickle cell disease (SCD) and beta-thalassemia, are prevalent diseases with variable clinical manifestation and severity that are thought to be governed, in part, by genetic modifiers. Despite the identification and characterization of a few putative genetic modifiers by previous studies, these are as yet insufficient to guide treatment recommendations or risk-stratify patients reliably. Also, it is expected that many additional genetic variants exist that can modify disease and its severity. This large-scale genome-wide association study (GWAS) will utilize SNP chips to investigate the genetic profile of individuals with hemoglobinopathies, thereby addressing the challenges of previous studies related to small sample sizes and low statistical power, while promoting the participation of diverse populations worldwide. The study aims to i) discover new genetic modifiers of hemoglobinopathies, ii) validate previously reported genetic modifiers, iii) pool and analyze existing genomic data, iv) standardize phenotypic descriptions, v) develop a research resource of disease-specific data generated in INHERENT, including genomic, phenotypic, and functional data, and vi) develop risk scores that can be used for patient stratification.
The main endpoints include:
- Worldwide demography, including numbers of patients, main genotypes, and overall disease severity/burden in participating centres
- Genetic modifiers affecting clinical or laboratory phenotypes of hemoglobinopathies, including
- overall survival in SCD and/or thalassemia,
- stroke and/or decreased neurocognitive function in SCD and/or thalassemia,
- renal impairment in SCD and/or thalassemia,
- leg ulcers in SCD,
- priapism in SCD,
- mild or severe acute pain and/or chronic pain syndromes in SCD,
- pulmonary hypertension in SCD and/or thalassemia,
- hyperhemolysis in SCD and/or thalassemia,
- fetal hemoglobin levels,
- degree of ineffective erythropoiesis,
- hepatic fibrosis/cirrhosis and/or cardiac siderosis,
- Genetic modifiers affecting response to treatment, including
- response to hydroxyurea,
- response to iron chelation treatment,
- response to emerging therapeutic agents
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cohort | – | Genetic: GWASIndividuals with hemoglobinopathies |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals diagnosed with an inherited hemoglobinopathy and are under regular follow-up in the participating centers
Key inclusion criteria (3 listed)
- Clinical diagnosis of an inherited hemoglobinopathy, including sickle cell disease (SCD), β-thalassemia, and α-thalassemia; all genotypes will be considered.
- Age ≥ 2 years old at the time of the collection of the phenotypic data.
- There will be no limits on study participants in terms of gender, ethnicity, morbidities.
Key exclusion criteria (3 listed)
- Patients treated with stem cell transplantation or genetic therapy.
- Age < 2 years old at the time of the collection of the phenotypic data.
- Patient or legal representative for minors unwilling or unable to give consent.
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 |
|---|---|---|
| GWASThe study will perform a GWAS experiments for all recruited subjects. The blood sample will be collected during routine clinical visits, only if DNA is not already available in existing biobanks. All individuals will provide consent for participation in the study. | Genetic | Cohort |
Primary outcome
Genetic modifiers in haemoglobinopathies through GWAS
Time frame: 5 years
Number of genetic variants (SNPs) associated with disease-specific phenotypes
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 20 Mar 2024.
- Background: PubMed 34406671Kountouris P, Stephanou C, Archer N, Bonifazi F, Giannuzzi V, Kuo KHM, Maggio A, Makani J, Manu-Pereira MDM, Michailidou K, Nkya S, Nnodu OE, Trompeter S, Tshilolo L, Wonkam A, Zilfalil BA, Inusa BPD, Kleanthous M; on behalf of the International Hemoglobinopathy Research Network (INHERENT). The International Hemoglobinopathy Research Network (INHERENT): An international initiative to study the role of genetic modifiers in hemoglobinopathies. Am J Hematol. 2021 Nov 1;96(11):E416-E420. doi: 10.1002/ajh.26323. Epub 2021 Aug 30. No abstract available.
- Official INHERENT websiteLink provided by the sponsor.
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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.
Petros Kountouris, PhD principal investigator
Cyprus Institute of Neurology and Genetics
26 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Disease and Thalassemia, Beta, run by Cyprus Institute of Neurology and Genetics at 26 sites in 16 countries.
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 3 inclusion and 3 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: looking for participants now, as of the sponsor's last update on 20 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Cyprus, Greece, Malaysia, Nigeria, United States and 11 more countries. 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. 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 Petros Kountouris, PhD (22392623 ext. 357, admin@inherentnetwork.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genetic modifiers in haemoglobinopathies through GWAS (time frame: 5 years). 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 NCT05799118, which also lists 1 linked publication.
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 20 Mar 2024.