Study of the Role of Genetic Modifiers in Hemoglobinopathies (INHERENT)

March 19, 2024 updated by: Petros Kountouris, PhD, Cyprus Institute of Neurology and Genetics
This study will investigate the role of genetic modifiers in hemoglobinopathies through a large-scale, multi-ethnic genome-wide association study (GWAS).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Observational

Enrollment (Estimated)

30000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Angola
      • Luanda, Angola
        • Recruiting
        • Lucrecia Paím Maternity
        • Contact:
          • Ligia Alves
  • Argentina
      • Buenos Aires, Argentina
        • Not yet recruiting
        • University of Buenos Aires
        • Contact:
          • Karen Scheps, PhD
  • Belgium
      • Leuven, Belgium
        • Not yet recruiting
        • University Hospitals Leuven
        • Contact:
          • Veerle Labarque, MD, PhD
  • Brunei Darussalam
      • Brunei, Brunei Darussalam
        • Not yet recruiting
        • Universiti Brunei Darussalam
        • Contact:
          • Mas Rina Wati Abdul Hamid
  • Congo, The Democratic Republic of the
      • Kinshasa, Congo, The Democratic Republic of the
        • Recruiting
        • Centre Hospitalier Monkole
        • Contact:
          • Leon Tshilolo, MD
  • Cyprus
      • Larnaca, Cyprus
        • Recruiting
        • Larnaca General Hospital
        • Contact:
          • Maria Sitarou, MD
      • Limassol, Cyprus
        • Recruiting
        • Limassol General Hospital
        • Contact:
          • Michael Hadjigavriel, MD
      • Nicosia, Cyprus
        • Recruiting
        • Archbishop Makarios III Hospital
        • Contact:
          • Soteroula Christou, MD
      • Paphos, Cyprus
        • Recruiting
        • Paphos General Hospital
        • Contact:
          • Thomas Dimitriou, MD
  • Denmark
      • Copenhagen, Denmark
        • Recruiting
        • Rigshospitalet
        • Contact:
          • Andreas Birkedal Glenthøj, MD
  • Greece
      • Athens, Greece
        • Recruiting
        • Laiko General Hospital
        • Contact:
          • Maria Dimopoulou, MD
      • Athens, Greece
        • Recruiting
        • Hippokrateio Hospital of Athens
        • Contact:
          • Sophia Delicou, MD
      • Athens, Greece
        • Not yet recruiting
        • National and Kapodistrian University of Athens
        • Contact:
          • Joanne Traeger-Synodinos, PhD
      • Larissa, Greece
        • Recruiting
        • General Hospital of Larissa
        • Contact:
          • Michael Diamantidis, MD
  • Israel
      • Afula, Israel
        • Not yet recruiting
        • Emek Medical Centre
        • Contact:
          • Ariel Koren, MD
  • Italy
      • Turin, Italy
        • Not yet recruiting
        • University of Turin
        • Contact:
          • Giorgia Mandrile, PhD
  • Malaysia
      • Ampang, Malaysia
        • Recruiting
        • Ampang Hospital
        • Contact:
          • Veena SELVARATNAM, MD
      • Bangi, Malaysia
        • Recruiting
        • Universiti Kebangsaan Malaysia
        • Contact:
          • Raja Zahratul Azma, MD
      • Kota Bharu, Malaysia
        • Recruiting
        • Universiti Sains Malaysia
        • Contact:
          • Bin Alwi Zilfalil, MD, PhD
  • Nigeria
      • Abuja, Nigeria
        • Recruiting
        • University of Abuja
        • Contact:
          • Obiageli E Nnodu, MD
      • Kaduna, Nigeria
        • Recruiting
        • Kaduna State University
        • Contact:
          • Livingstone Dogara, MD
      • Zaria, Nigeria
        • Recruiting
        • Ahmadu Bello University
        • Contact:
          • Aliyu Waziri, MD
  • Pakistan
      • Lahore, Pakistan
        • Not yet recruiting
        • University of Lahore
        • Contact:
          • Ahmed Bilal, PhD
  • Portugal
      • Coimbra, Portugal
        • Not yet recruiting
        • Centro Hospitalar e Universitario de Coimbra
        • Contact:
          • Celeste Bento, PhD
  • Spain
      • Madrid, Spain
        • Not yet recruiting
        • Hospital Clinico San Carlos
        • Contact:
          • Paloma Ropero, PhD
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Boston Children's Hospital
        • Contact:
          • Natasha Archer, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Individuals diagnosed with an inherited hemoglobinopathy and are under regular follow-up in the participating centers

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort
Individuals with hemoglobinopathies
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic modifiers in haemoglobinopathies through GWAS
Time Frame: 5 years
Number of genetic variants (SNPs) associated with disease-specific phenotypes
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cyprus Institute of Neurology and Genetics

Investigators

  • Principal Investigator: Petros Kountouris, PhD, Cyprus Institute of Neurology and Genetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2022

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

September 30, 2027

Study Registration Dates

First Submitted

March 10, 2023

First Submitted That Met QC Criteria

March 22, 2023

First Posted (Actual)

April 5, 2023

Study Record Updates

Last Update Posted (Actual)

March 20, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1 (Mobile Health and Wellness Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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