Cerebral Palsy Clinical Trial
— NIBS-CPOfficial title:
Neuroimaging of Babies During Natural Sleep to Assess Typical Development and Cerebral Palsy
Background: Early diagnosis of cerebral palsy (CP) is crucial, enabling intervention when neuroplasticity is at its highest. Magnetic resonance imaging (MRI) plays a vital role in CP diagnosis. Currently, diagnostic MRI of newborns and infants with suspected brain damage relies heavily on structural MR images. The current study aims to i) establish procedures for clinical infant and toddler MRI during natural sleep, ii) use advanced MRI sequences, such as advanced diffusion-weighted imaging (DWI), that may be more sensitive in detecting early brain damage, and iii) map relationships between early brain development, and motor function and development. Methods: The NIBS-CP study will enroll approximately 200 infants either at risk for CP or typically developing. Infants will be followed longitudinally (for three waves) between 3 months and 2 years of age with cerebral MRI at 3 Tesla and comprehensive assessments of motor and cognitive functioning. The MRI protocol includes advanced diffusion-weighted imaging, high-resolution structural MRI, and MR spectroscopy. The motor and cognitive assessments include Hand Assessment in Infants, Alberta Infant Motor Scales, Hammersmith Infant Neurological Examination, Peabody Developmental Motor Scales, Bayley Scales of Infant Development, and Ages and Stages Questionnaires. NIBS-CP aims to establish normative material on early brain development of Danish children and conduct normative modeling of typical and atypical development to identify deviations in brain development at the level of the single child. Discussion: Identifying predictive brain structural features of motor function and motor development is key to the future use of early MRI in the clinical work-up, as this promotes early diagnosis and (clinical) intervention strategies tailored to the individual child.
Status | Not yet recruiting |
Enrollment | 200 |
Est. completion date | December 31, 2027 |
Est. primary completion date | December 31, 2027 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 2 Months to 11 Months |
Eligibility | Inclusion Criteria High-Risk population: Group: 'Newborn-detectable risk-pathway' - Preterm birth with gestational age below 32 weeks - Birth weight below 1500 g - Moderate to severe brain injury (A label of moderate to severe brain injury was considered if there was Papile grade three to four intraventricular haemorrhage, cystic periventricular leukomalacia, neonatal stroke, term hypoxic-ischaemic encephalopathy (=35 weeks gestation at birth) or other significant neurological condition) - History (e.g., neonatal seizures, ECMO, meningitis, kernicterus, severe hypoglycemia) or neurological risk factors (malformations in CNS, increased tone) Group: 'Infant detectable risk-pathway' - Inability to sit independently by age 9 months - Hand function asymmetry or crawl asymmetry - Inability to take weight through the plantar surface of the feet - History (e.g., as above) or neurological risk factors Additional inclusion criteria for inclusion in NIBS-CP for both CP-risk groups: - Consent to health-relevant information on clinical findings being passed on to the medical doctors in CP-EDIT and/or their primary care physician. Inclusion Criteria Typically developing infant population: - Born >37 weeks - Uneventful birth - No known history of brain injury - No neurological condition - Consent to health-relevant information on clinical findings being passed on to their primary care physician or relevant medical doctors, e.g., neuropaediatrician. Exclusion Criteria (all groups): - Infants have any MRI contraindications, e.g., pacemaker or other implanted electronic devices. - Families do not speak or understand Danish. - Families do not wish to be informed about incidental findings on the MRI, or scores within the clinical range in the neurological, motor, or cognitive assessments. |
Country | Name | City | State |
---|---|---|---|
Denmark | Danish Research Centre for Magnetic Resonance | Hvidovre | Capital Region |
Lead Sponsor | Collaborator |
---|---|
Danish Research Centre for Magnetic Resonance | Department of Pediatrics and Adolescent Medicine, Hvidovre Hospital, Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Department of Physical- and Occupational Therapy; Hvidovre Hospital |
Denmark,
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Rutherford S, Barkema P, Tso IF, Sripada C, Beckmann CF, Ruhe HG, Marquand AF. Evidence for embracing normative modeling. Elife. 2023 Mar 13;12:e85082. doi: 10.7554/eLife.85082. — View Citation
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Wagenaar N, Verhage CH, de Vries LS, van Gasselt BPL, Koopman C, Leemans A, Groenendaal F, Benders MJNL, van der Aa NE. Early prediction of unilateral cerebral palsy in infants at risk: MRI versus the hand assessment for infants. Pediatr Res. 2020 Apr;87(5):932-939. doi: 10.1038/s41390-019-0664-5. Epub 2019 Nov 13. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Diffusion-weighted magnetic resonance imaging | Microstructural measures obtained from fixel-based and tensor-based analysis. | Baseline, 12 months, 24 months | |
Primary | Brain volumetric measures | Total brain volume, cortex volume, and white matter volume, as well as regional grey matter volume of cortical parcels and subcortical grey matter structures measured in mm3 | Baseline, 12 months, 24 months | |
Primary | Cortical thickness | Global and regional measures of apparent cortical thickness measured in mm | Baseline, 12 months, 24 months | |
Primary | Brain connectivity measures | Brain connectivity measures obtained from structural covariance and tractography-based connectivity analyses | Baseline, 12 months, 24 months | |
Primary | Indices of myelination | T1/T2 contrast in grey and white matter regions | Baseline, 12 months, 24 months | |
Primary | MR-spectroscopy measures | Brain metabolic measures (metabolites: NAA, choline, creatine, myoinositol, lactate) obtained from voxels containing the basal ganglia and thalamus in the left and right hemispheres. | Baseline, 12 months, 24 months | |
Primary | Surface area | Global and regional surface area measured in mm2 | Baseline, 12 months, 24 months | |
Secondary | Hand assessment for infants (HAI) | The HAI measures the degree and quality of goal-directed actions performed with each hand separately as well as with both hands together. The HAI is scored on 17 items (12 unimanual and 5 bimanual) | Baseline, 12 months | |
Secondary | Alberta Infant Motor Scale (AIMS) | The AIMS is an observational assessment scale that measures gross motor maturation in infants from birth through independent walking. The scale consists of 58 items organized into four positions: prone, supine, sitting, and standing. Each item describes three aspects of motor performance - weight-bearing, posture, and antigravity movements. | Baseline, 12 months | |
Secondary | Peabody Developmental Motor Scales (PDMS-2) | PDMS-2 is an in-depth assessment of gross and fine motor skills of children from birth through 5 years. | 24 months | |
Secondary | Bayley Scales of Infant and Toddler Development, Fourth Edition (BSID-4) | BSID-4 is a standardized and norm-referenced assessment that measures the cognitive, motor, language, and social-emotional development of infants and toddlers aged 0-3 years. | 24 months | |
Secondary | Ages & Stages (ASQ) | ASQ is a parent-rated questionnaire for screening young children's developmental milestones between the ages of 1 month to 5½ years. There are two main questionnaires, one assessing motor and cognitive development and one assessing socio-emotional development. | 12 months, 24 months | |
Secondary | Hammersmith Infant Neurological Examination (HINE) | HINE is a standardized and scorable neurological examination used in the diagnosis of CP up to the age of 24 months. The HINE detects CP with more than 90% accuracy and provides objective information about severity. | Baseline, 24 months |
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