Study of the Role of Genetic Modifiers in Hemoglobinopathies
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: GWAS.
- Who it may be relevant to
- Registry conditions: Sickle Cell Disease, Thalassemia, Beta, Thalassemia Alpha, Hemoglobinopathies. Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Angola, Argentina, Belgium, Brunei +11
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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:
1. Worldwide demography, including numbers of patients, main genotypes, and overall disease severity/burden in participating centres 2. Genetic modifiers affecting clinical or laboratory phenotypes of hemoglobinopathies, including
1. overall survival in SCD and/or thalassemia, 2. stroke and/or decreased neurocognitive function in SCD and/or thalassemia, 3. renal impairment in SCD and/or thalassemia, 4. leg ulcers in SCD, 5. priapism in SCD, 6. mild or severe acute pain and/or chronic pain syndromes in SCD, 7. pulmonary hypertension in SCD and/or thalassemia, 8. hyperhemolysis in SCD and/or thalassemia, 9. fetal hemoglobin levels, 10. degree of ineffective erythropoiesis, 11. hepatic fibrosis/cirrhosis and/or cardiac siderosis, 3. Genetic modifiers affecting response to treatment, including
1. response to hydroxyurea, 2. response to iron chelation treatment, 3. response to emerging therapeutic agents
Interventions
- Genetic GWAS
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.
Primary outcome measures
- Genetic modifiers in haemoglobinopathies through GWAS [Time frame: 5 years]
Eligibility criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Cyprus · 4 centers
- Larnaca General Hospital — Larnaca
- Limassol General Hospital — Limassol
- Archbishop Makarios III Hospital — Nicosia
- Paphos General Hospital — Paphos
Greece · 4 centers
- Hippokrateio Hospital of Athens — Athens
- Laiko General Hospital — Athens
- National and Kapodistrian University of Athens — Athens
- General Hospital of Larissa — Larissa
Malaysia · 3 centers
- Ampang Hospital — Ampang
- Universiti Kebangsaan Malaysia — Bangi
- Universiti Sains Malaysia — Kota Bharu
Nigeria · 3 centers
- University of Abuja — Abuja
- Kaduna State University — Kaduna
- Ahmadu Bello University — Zaria
United States · 1 center
- Boston Children's Hospital — Boston
Angola · 1 center
- Lucrecia Paím Maternity — Luanda
Argentina · 1 center
- University of Buenos Aires — Buenos Aires
Belgium · 1 center
- University Hospitals Leuven — Leuven
Brunei · 1 center
- Universiti Brunei Darussalam — Brunei
Democratic Republic of the Congo · 1 center
- Centre Hospitalier Monkole — Kinshasa
Denmark · 1 center
- Rigshospitalet — Copenhagen
Israel · 1 center
- Emek Medical Centre — Afula
Italy · 1 center
- University of Turin — Turin
Pakistan · 1 center
- University of Lahore — Lahore
Portugal · 1 center
- Centro Hospitalar e Universitário de Coimbra — Coimbra
Spain · 1 center
- Hospital Clínico San Carlos — Madrid
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 rol PMID 34406671
Identifiers
NCT: NCT05799118 · 1