Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05564845 |
| Other study ID # |
MEC-25022-0004 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 20, 2022 |
| Est. completion date |
July 1, 2025 |
Study information
| Verified date |
September 2022 |
| Source |
Erasmus Medical Center |
| Contact |
Aida Kidane |
| Phone |
+3110-7036691 |
| Email |
a.kidanegebremeskel[@]erasmusmc.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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.
Description:
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.
