Brain Structure and Neurocognitive Development in Sickle Cell Disease; a Longitudinal Cohort Study (BRICK Study)

NCT05564845 | Unknown

• 1 other identifier: MEC-25022-0004
• Study Type: observational
• Target: 84
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Brain Development Abnormality; Sickle Cell Disease

Keywords

brain development; Sickle cell disease

Outcome Measures

Primary Outcomes (1)

• mm3/time unit

  Total white matter volume increase in children and adolescents with SCD

  4 years

Secondary Outcomes (8)

• Full scale IQ (FSIQ)

  4 years

• Incidence of stroke

  4 years

• Other forms complications due to SCD

  4 years

• Amount of hospital admissions

  4 years

• Ld, bilirubin

  4 years

Study Arms (2)

Severe SCD genotypes

Children between 6 and 18 years of age of genotypes HbSS, HbSβº

Diagnostic Test: MR scan of the brain; Diagnostic Test: Blood work; Diagnostic Test: Neurological examination; Diagnostic Test: Neuropsychological assessment

Not severe SCD genotypes

Children between 6 and 18 years of age of genotypes HbSβ+, and HbSC and more

Diagnostic Test: MR scan of the brain; Diagnostic Test: Blood work; Diagnostic Test: Neurological examination; Diagnostic Test: Neuropsychological assessment

Interventions

MR scan of the brain DIAGNOSTIC_TEST

Subjects will undergo MRI of the head, blood sampling and neurological examination on the same day or spread over 2 days. On a separate day from blood sampling and undergoing an MRI scan, the neuropsychological assessment will take place. The interval between the MRI scan and the neuropsychological assessment will be a maximum of 2 months. These measurements will be performed a total of 3 times with an interval of 2 years.

Not severe SCD genotypes; Severe SCD genotypes

Blood work DIAGNOSTIC_TEST

Lab work for current lab values and biobanking

Not severe SCD genotypes; Severe SCD genotypes

Neurological examination DIAGNOSTIC_TEST

Classical neurological examination

Not severe SCD genotypes; Severe SCD genotypes

Neuropsychological assessment DIAGNOSTIC_TEST

Overview of standard neurocognitive assessment tools in BRICK study Children and adolescents (Young) Adults * Wechsler Intelligence Test for Children- Fifth edition (WISC-V) (6-16 YOA) Wechsler Adult Intelligence Scale- Fourth edition WAIS-IV (16-24 YOA) * A Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II) * Narrative memory * Word fluency * Route finding NEPSY-II * World Fluency * Additional Questionnaires (6-18 years): * Child Behavior Checklist (CBCL) * Teacher Report Form (TRF) * Youth Self Report (YSR) * Behavior Rating Inventory of Executive Function (BRIEF), parent- and teacher-report) * Conners-3® • Additional Questionnaires (18+ years): * Adult Self-Report (ASR) / Adult Behavior Checklist (ABCL) (in case of IQ\<70) * Behavior Rating Inventory of Executive Function Adult version (BRIEF-A), self-report / informant-report (in case of IQ\<70) * Conners' Adult ADHD Rating Scales (CAARS) Emma toolbox

Not severe SCD genotypes; Severe SCD genotypes

Eligibility Criteria

• Age: 6 Years - 25 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children and adolescents diagnosed with SCD of all genotypes, treated at Erasmus MC and the Amsterdam UMC, ranging from 6 to 18 years at initiation of the study. The clinical phenotype of SCD consists of a spectrum: From the patients with a high hemoglobin plus an absent or lower incidence of VOCs to the patients with a higher hemoglobin and a higher incidence of VOCs. We chose to include SCD patients of all genotypes, not only the HbSS and Hbẞ0 thalassemia, to cover the whole phenotypic range of SCD. This was chosen in order to infer the possible causes of an expected difference in white matter volume increase, like anemia and sickling-propensity.

You may qualify if:

• Patients with SCD of all genotype between 6 and 18 at baseline

You may not qualify if:

• Parents/ guardians (in case of minors) or patients themselves (\>16 years) unable to make an informed decision on participating in this study.
• An abnormal brain MRI prior to initiation of the study due to non-SCD related causes.
• Contraindications for brain MRI per protocol

Sponsors & Collaborators

• Dr. Marjon H. Cnossen MD PhD: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (2)

Erasmus MC

Rotterdam, South Holland, 3000 CA, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, Netherlands

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Biobanking will take place prospectively

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Neurologic Examination

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

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Physical Examination

Central Study Contacts

Aida Kidane

CONTACT

+3110-7036691; a.kidanegebremeskel@erasmusmc.nl

Marjon Cnossen

CONTACT

+310-7036691; m.cnossen@erasmusmc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: October 4, 2022
• Study Start: June 20, 2022
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: October 4, 2022

Record last verified: 2022-09

Locations

NL (2)