Genetic and Haematological Modifiers of SCD Severity in Kaduna State, Northern Nigeria (SCA)
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ClinicalTrials.gov Identifier: NCT05837871 |
Recruitment Status :
Not yet recruiting
First Posted : May 1, 2023
Last Update Posted : May 1, 2023
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Tracking Information | |||||||||||||
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First Submitted Date | March 14, 2023 | ||||||||||||
First Posted Date | May 1, 2023 | ||||||||||||
Last Update Posted Date | May 1, 2023 | ||||||||||||
Estimated Study Start Date | May 1, 2023 | ||||||||||||
Estimated Primary Completion Date | May 1, 2025 (Final data collection date for primary outcome measure) | ||||||||||||
Current Primary Outcome Measures |
Cross sectional arm [ Time Frame: 3 months ] Subjects with Sickle Cell disease (n=200), aged 2 - 18 years will be recruited for this arm of the study
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Original Primary Outcome Measures | Same as current | ||||||||||||
Change History | No Changes Posted | ||||||||||||
Current Secondary Outcome Measures |
Longitudinal arm [ Time Frame: 18 months ] Subjects with SCD (n=200) at 9 months of age will be recruited and followed up at 12months, 18months and 24months
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Original Secondary Outcome Measures | Same as current | ||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||
Descriptive Information | |||||||||||||
Brief Title | Genetic and Haematological Modifiers of SCD Severity in Kaduna State, Northern Nigeria | ||||||||||||
Official Title | Assessment of Genetic and Haematological Modifiers of Disease Severity Among Patients With Sickle Cell Disease (SCD) in Kaduna State, Northern Nigeria | ||||||||||||
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). |
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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 Glu>Val), 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, i.e. 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 (e.g., 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 and/or therapeutic targets for investigation towards improved patient management and treatment. |
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Study Type | Observational | ||||||||||||
Study Design | Observational Model: Family-Based Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||||||||||
Biospecimen | Retention: Samples With DNA Description: Whole peripheral blood sample and Extracted DNA from peripheral mononuclear cells
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Sampling Method | Probability Sample | ||||||||||||
Study Population | Patients with Sickle Cell Anaemia attending Clinics in Ahmadu Bello University Teaching Hospital, Zaria Nigeria. | ||||||||||||
Condition | Sickle Cell Disease | ||||||||||||
Intervention | Not Provided | ||||||||||||
Study Groups/Cohorts |
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Publications * | Not Provided | ||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||
Recruitment Status | Not yet recruiting | ||||||||||||
Estimated Enrollment |
400 | ||||||||||||
Original Estimated Enrollment | Same as current | ||||||||||||
Estimated Study Completion Date | June 1, 2025 | ||||||||||||
Estimated Primary Completion Date | May 1, 2025 (Final data collection date for primary outcome measure) | ||||||||||||
Eligibility Criteria | Inclusion Criteria:
(ii) Patients in steady-state and in sickle cell crisis.
(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. Exclusion Criteria:
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Sex/Gender |
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Ages | 9 Months to 18 Years (Child, Adult) | ||||||||||||
Accepts Healthy Volunteers | No | ||||||||||||
Contacts |
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Listed Location Countries | Not Provided | ||||||||||||
Removed Location Countries | |||||||||||||
Administrative Information | |||||||||||||
NCT Number | NCT05837871 | ||||||||||||
Other Study ID Numbers | ABUTH | ||||||||||||
Has Data Monitoring Committee | Yes | ||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement |
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Current Responsible Party | Bello Jamoh Yusuf, Ahmadu Bello University Teaching Hospital | ||||||||||||
Original Responsible Party | Same as current | ||||||||||||
Current Study Sponsor | Ahmadu Bello University Teaching Hospital | ||||||||||||
Original Study Sponsor | Same as current | ||||||||||||
Collaborators | Cyprus Institute of Neurology and Genetics | ||||||||||||
Investigators | Not Provided | ||||||||||||
PRS Account | Ahmadu Bello University Teaching Hospital | ||||||||||||
Verification Date | April 2023 |