Brain Development AbnormalityBRICKNCT05564845
Brain Structure and Neurocognitive Development in Sickle Cell Disease; a Longitudinal Cohort Study (BRICK Study)
An observational study of Brain Development Abnormality and Sickle Cell Disease, run by Dr. Marjon H. Cnossen MD PhD at 2 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 6 to 25 years
- Conditions the study is for
- Brain Development Abnormality, Sickle Cell Disease
- What is being tested?
- MR scan of the brain, Blood work and Neurological examination
- Type of treatment
- Injection or infusion
- How many people
- 84 participants
- Where
- 2 sitesNetherlands
- Study dates
- 20 Jun 2022to 1 Jul 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 25 years
- All sexes
- Child, Adult
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.
Who may be able to join
- Patients with SCD of all genotype between 6 and 18 at baseline
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites, 2 recruiting
- Not yet recruiting
Amsterdam University Medical Center
Amsterdam
Noa IJdo, n.ijdo@amsterdamumc.nl
Karin Fijnvandraat, MD, PhD
- Recruiting
Erasmus MC
Rotterdam, South Holland, 3000 CA
Aida Kidane, a.kidanegebremeskel@erasmusmc.nl
Marjon Cnossen, MD, PhD
About this 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.
Read the detailed 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.
- Conditions
- Brain Development Abnormality, Sickle Cell Disease
- Being tested
- MR scan of the brain, Blood work, Neurological examination, Neuropsychological assessment
- Keywords
- brain development, Sickle cell disease
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR scan of the brainDiagnostic 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.
Blood workDiagnostic test
Lab work for current lab values and biobanking
Neurological examinationDiagnostic test
Classical neurological examination
Neuropsychological assessmentDiagnostic 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
| Study group | Role | What they receive |
|---|---|---|
| Severe SCD genotypes | Children between 6 and 18 years of age of genotypes HbSS, HbSβº Receives: 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 Receives: Diagnostic Test: MR scan of the brain; Diagnostic Test: Blood work; Diagnostic Test: Neurological examination; Diagnostic Test: Neuropsychological assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
mm3/time unit
Total white matter volume increase in children and adolescents with SCD
Measured: 4 years
Secondary outcomes (8)
Full scale IQ (FSIQ)
Neurocognitive functioning (intelligence, specific neurocognitive functions, network organization)
Measured: 4 years
Incidence of stroke
Measured: 4 years
Other forms complications due to SCD
Measured: 4 years
Amount of hospital admissions
Measured: 4 years
Ld, bilirubin
Hemolysis biomarkers
Measured: 4 years
Times/year
ER visits
Measured: 4 years
Hb, Ht
Biomarkers for anemia
Measured: 4 years
T score metric: a score of 50 represents the mean score of a reference population and 10 is the standard deviation.
Patient-Reported Outcomes Measurement Information System® (PROMIS) within domains such as fatigue, pain behavior, depression, anxiety
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2022
- Study start20 Jun 2022
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Development AbnormalityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr. Marjon H. Cnossen MD PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. Marjon H. Cnossen MD PhD, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05564845
- Sponsor's protocol ID
- MEC-25022-0004
- Acronym
- BRICK
- Status last verified
- Sep 2022
- First submitted
- 21 Sep 2022
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Structure and Neurocognitive Development in Sickle Cell Disease; a Longitudinal Cohort Study (BRICK Study)
- ClinicalTrials.gov ID
- NCT05564845
- Acronym / sponsor ID
- BRICK / MEC-25022-0004
- Conditions
- Brain Development Abnormality, Sickle Cell Disease
- Keywords
- brain development, Sickle cell disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Dr. Marjon H. Cnossen MD PhDUniversity, hospital or other
- Collaborators
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- 20 Jun 2022 (actual)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 4 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Severe SCD genotypes | – | Diagnostic Test: MR scan of the brain, Diagnostic Test: Blood work, Diagnostic Test: Neurological examination, Diagnostic Test: Neuropsychological assessmentChildren between 6 and 18 years of age of genotypes HbSS, HbSβº |
| Not severe SCD genotypes | – | Diagnostic Test: MR scan of the brain, Diagnostic Test: Blood work, Diagnostic Test: Neurological examination, Diagnostic Test: Neuropsychological assessmentChildren between 6 and 18 years of age of genotypes HbSβ+, and HbSC and more |
Who may qualify
- Ages
- 6 to 25 years
- Sex
- All
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (1 listed)
- Patients with SCD of all genotype between 6 and 18 at baseline
Key exclusion criteria (3 listed)
- Parents/ guardians (in case of minors) or patients themselves (>16 years) unable to make an informed decision on participating in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MR scan of the brainSubjects 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. | Diagnostic test | Not severe SCD genotypes, Severe SCD genotypes |
| Blood workLab work for current lab values and biobanking | Diagnostic test | Not severe SCD genotypes, Severe SCD genotypes |
| Neurological examinationClassical neurological examination | Diagnostic test | Not severe SCD genotypes, Severe SCD genotypes |
| Neuropsychological assessmentOverview 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 | Diagnostic test | Not severe SCD genotypes, Severe SCD genotypes |
Primary outcome
mm3/time unit
Time frame: 4 years
Total white matter volume increase in children and adolescents with SCD
8 secondary outcomes
Full scale IQ (FSIQ)
Time frame: 4 years
Incidence of stroke
Time frame: 4 years
Other forms complications due to SCD
Time frame: 4 years
Amount of hospital admissions
Time frame: 4 years
Ld, bilirubin
Time frame: 4 years
Times/year
Time frame: 4 years
Hb, Ht
Time frame: 4 years
T score metric: a score of 50 represents the mean score of a reference population and 10 is the standard deviation.
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Development Abnormality and Sickle Cell Disease, run by Dr. Marjon H. Cnossen MD PhD at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aida Kidane (+3110-7036691, a.kidanegebremeskel@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mm3/time unit (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2022.