Genetic and Haematological Modifiers of SCD Severity in Kaduna State, Northern Nigeria

NCT05837871 | Unknown DMC

• 1 other identifier: ABUTH
• Study Type: observational
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is aimed to assess the genetic and haematological modifiers of disease severity among patients with Sickle Cell Disease (SCD) in Kaduna State, northern Nigeria. It is composed by two separate study designs: a cross-sectional study and a longitudinal study. The cross-sectional study will evaluate clinical and laboratory parameters in paediatric Sickle Cell Anaemia (SCA) patients (ages 2-18 years) in steady state and during Vaso-Occlusive Crisis (VOCs) to determine the parameters that can be used as a guide to monitor the course of the disease towards early recognition and management of sickle cell crises. In addition, the study will explore genotype-phenotype correlations in SCA patients by targeted Next-Generation Sequencing (NGS) of genetic modifiers for haemoglobinopathies. The longitudinal study will collect clinical and laboratory data over time for a paediatric cohort of SCD patients (9 months old; followed up to 2 years of age) and parental samples will be collected to determine the βS-globin haplotype in family trios. The aim is to determine the temporal relationships among foetal haemoglobin (HbF) levels, haematological parameters and frequency of sickle cell crises in SCD patients in relation to the type of the βS-globin haplotype and the sickle genotype. In addition, samples collected at 24 months of age will also be analysed by NGS to identify genetic modifiers of clinical manifestations and severity of SCA. Participants from the following centre will be involved: Ahmadu Bello University Teaching Hospital (ABUTH) Zaria. Consent from all the study parents/legally designated representatives as well as assent from minors will be sought. Consent for genetic analyses will be sought as well. Clinical and haematological analyses will be performed at ABUTH while genetic analyses will be performed at the Cyprus Institute of Neurology and Genetics (CING).

Conditions

Sickle Cell Disease

Keywords

Genetics; Haematological parameters; Modifiers; Sickle Cell Disease; Kaduna, Nigeria; Assessment

Outcome Measures

Primary Outcomes (1)

• Cross sectional arm

  Subjects with Sickle Cell disease (n=200), aged 2 - 18 years will be recruited for this arm of the study * Clinical severity using the severity index developed by van den Tweel et al in PMID 20806231 * Complete blood count using Coulter Haematology Auto-analyzer: WBC (10\^9/L), RBC (10\^12/L), Hb (g/L), HCT (%), PLT (10\^9/L), MCV (fl), MCH (pg), MCHC (g/L) * Foetal haemoglobin using HPLC - 10 machine: (%) * Hemoglobin haplotype using a SNPs test \[RFLP-PCR\] to determine beta S-globin haplotypes

  3 months

Secondary Outcomes (1)

• Longitudinal arm

  18 months

Study Arms (2)

Cross sectional arm

Patients with Sickle Cell Anaemia aged 2 to 18 years. Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype

Longitudinal arm

* Patients with Sickle Cell Anaemia recruited at 9 months of age then followed up at 12 months, 18 months and 24 months. * Assessed for clinical severity, Complete Blood Count, foetal haemoglobin and Haemoglobin Haplotype * Both parents assesed for Haemoglobin Haplotype * Genotype - Haplotype assessment to be carried out

Eligibility Criteria

• Age: 9 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Patients with Sickle Cell Anaemia attending Clinics in Ahmadu Bello University Teaching Hospital, Zaria Nigeria.

You may qualify if:

• (i) Paediatric patients (ages 2-18 years) with known HbSS genotype from case records. They will be recruited during routine visits at the haematology clinics.
• (ii) Patients in steady-state and in sickle cell crisis.
• Patients will be considered to be in steady-state if they are in a period free of crisis extending from at least three weeks since the last clinical event and three months or more since the last blood transfusion, to at least one week before the start of a new clinical event.
• Patients will be considered to be in sickle cell crisis (i.e. vaso-occlusive crisis, VOC) if they are known to have SCD, together with bone or joint pain, or multiple sites of pain, necessitating hospital admission and analgesic administration.
• (iii) Paediatric patients enrolled at 3 months of age with SCD diagnosed during newborn screening and followed over time at 6 months, 9 months, 12 months and 24 months of age.
• (iv) A written informed consent signed by all participants and/or parents/legally designated representatives is required to be recruited.

You may not qualify if:

• (i) Subjects with overt features of significant co-morbidities like malignancies, malnutrition, congenital deficiencies or severe infections.

Sponsors & Collaborators

• Ahmadu Bello University Teaching Hospital: lead
• Cyprus Institute of Neurology and Genetics: collaborator

Biospecimen

Retention: SAMPLES WITH DNA

Whole peripheral blood sample and Extracted DNA from peripheral mononuclear cells

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Bello Jamoh Yusuf, Dr

CONTACT

08033733152; bjamoh@yahoo.com

Hafsa AR Prof

CONTACT

08039625612; hafsahahmad1@gmail.com

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: May 1, 2023
• Study Start: May 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: May 1, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be available in 2 years with limitless access