Ignite Creation Date:
2024-05-06 @ 6:56 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05837871
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-05-01
First Post:
2023-03-14
Brief Title:
Genetic and Haematological Modifiers of SCD Severity in Kaduna State Northern Nigeria
Sponsor:
Ahmadu Bello University Teaching Hospital
Organization:
Ahmadu Bello University Teaching Hospital
Study Overview
Official Title:
Assessment of Genetic and Haematological Modifiers of Disease Severity Among Patients With Sickle Cell Disease SCD in Kaduna State Northern Nigeria
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SCA
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 parentslegally 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
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 parentslegally 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
Detailed Description:
Sickle cell anaemia SCA is a multisystem disorder with massive medical social and financial implications worldwide It is caused by a single mutation in the β-globin gene β6 GluVal which leads to the production of abnormal sickle haemoglobin HbS Africa is the major origin of the sickle βS mutation which occurs on diverse genetic haplotype backgrounds SCA has a Mendelian pattern of inheritance βS gene homozygosity ie HbSS Although all SCA patients share the same genetic mutation the disease exhibits wide heterogeneity in clinical expression which can be explained by both environmental and genetic factors The environmental factors include infections trauma climate temperature and humidity and air quality as well as socioeconomic factors many of which are controllable The genetic factors on the other hand cannot be controlled The best-characterized genetic factors include variants in the genes associated with foetal haemoglobin HbF production co-inheritance of alpha-thalassaemia sickle genotype and the type of βS-globin haplotype The role of other potential genetic modifiers is less clear particularly with regards to sickle cell disease related organ damage eg risk for stroke haemolysis and acute chest syndrome
Understanding the molecular basis of clinical heterogeneity and disease severity for SCA can have direct clinical applications for prognosis via risk stratification of patients also facilitating the use of personalized targeted therapeutic interventions As a turning-point in genomics the advent of high-throughput sequencing and whole-genome analysis has made it feasible to discover hitherto unsuspected variants that could add to current understanding of genotype-phenotype relationships in SCA The identification of modifying genetic variants might suggest new prognostic andor therapeutic targets for investigation towards improved patient management and treatment
Understanding the molecular basis of clinical heterogeneity and disease severity for SCA can have direct clinical applications for prognosis via risk stratification of patients also facilitating the use of personalized targeted therapeutic interventions As a turning-point in genomics the advent of high-throughput sequencing and whole-genome analysis has made it feasible to discover hitherto unsuspected variants that could add to current understanding of genotype-phenotype relationships in SCA The identification of modifying genetic variants might suggest new prognostic andor therapeutic targets for investigation towards improved patient management and treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None