Sickle Cell Disease Clinical Trial
Official title:
Brain Structure and Neurocognitive Development in Sickle Cell Disease; a Longitudinal Cohort Study (BRICK Study)
Sickle cell disease (SCD) is an autosomal recessive red blood cell blood disorder. One especially vital organ affected in SCD is the brain. Individuals with SCD have an increased risk of both overt cerebral infarctions and silent infarctions. The latter are brain lesions without apparent neurological sequelae. Since cortical neurons in the brain lack the ability to regenerate, tissue damage accumulates throughout the already shortened lifespan of individuals with SCD, resulting in far-reaching consequences such as significant cognitive impairment. Currently, only hematological stem cell transplantation can halt the multiorgan tissue damage. However, the criteria to determine the timing of curative therapy do not center the brain, despite that subtle anomalies of this critical organ can have long-lasting consequences. Since it is not yet known whether brain tissue damage precedes, parallels, or lags behind non-brain tissue damage, it is critical to map these effects in youth with SCD. While importantly comparing images with a healthy reference population. Understanding how the brain is affected is critical for clinical decision making, such as timing of potentially curative interventions but also, to prevent long term irreversible brain damage in youth with SCD. In this study, a cohort of 84 SCD patients between the ages of 6 and 18 at baseline, will undergo MR imaging, neurological examination, neuropsychological assessment and blood sampling three times in total, with intervals of two years; results will be innovatively compared with children included in the Generation R population study (±8000 MRIs children and (young)adults) 6-20 years of age). Our hypothesis, based on the inability of the brain to generate new cortical neurons following cell death, is that brain function is impaired earlier than other organ systems and that there is an age-dependent limit in the brain's ability to remodel itself based on neuroplasticity.
Objective: The primary objective is to evaluate longitudinal developmental changes in brain structure in patients aged 6-18 years with SCD. The secondary objective is to analyze the longitudinal relations between biomarkers, demographic characteristics, brain structure, neurocognitive functioning, behavioral functioning and developmental changes in brain structure. Study Design: Longitudinal cohort study (BRICK) with a duration of 4 years. Study population: Children and adolescents with sickle cell disease (SCD) of all genotypes (e.g. HbSS, HbSβº, HbSβ+, and HbSC) aged 6 -18 years. This will be compared to a cohort of healthy children and adolescents from Generation R. Primary study endpoint: - Total white matter volume increase in children and adolescents with SCD Secondary study endpoints - Neurocognitive functioning (intelligence, specific neurocognitive functions, network organization) - Incidence of stroke - Other forms complications due to SCD - Amount of hospital admissions, day care admissions (adult care only), crises at home, contact moments with the sickle cell center, ER visits - Biomarkers for anemia, hemolysis, inflammation and endothelial activation. - Behavioral functioning Nature and extent of the burden and risk associated with participation, benefit and group relatedness: By creating an advanced model for structural neurological, neurocognitive functioning in SCD, we will gain more insight into the pathophysiological origins and risk factors for SCD-related brain abnormalities. This will support development of preventive and supportive strategies as well as the initiation and evaluation of therapeutic interventions. Previous experience with the performance of brain MRI scans combined with recent research, indicates that the emotional burden placed on young children when undergoing a brain MR scan, are proportionate to the emotional burden placed on adults when they undergo a brain MR-scan. Furthermore, children will be offered the opportunity to become acquainted with the research procedure by witnessing an MRI scan session prior before participation. ;
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