Clinical trial NCT05013736: Baby Brain Recovery Study
Official title: Perinatal Stroke: Longitudinal Assessment of Infant Brain Organization and Recovery Through Neuroexcitability, Neuroimaging and Motor Development
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Perinatal Stroke
Keywords: Magnetic Resonance Imaging (MRI)
Brain Reorganization
Brain Lesions
perinatal stroke
neonatal hemorrhagic stroke
neonatal thrombotic stroke
neonatal intracranial hemorrhage
neonatal periventricular leukomalacia
hypoxic ischemic encephalopathy
neonatal brain bleed
early brain injury
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2021-08-19
Enrollment: 65
Sex: ALL
Minimum age (years): 0
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pre-term and term born infants with corrected gestational age between term age and 24 months with radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, or periventricular leukomalacia. Parents/legal guardians and infants able to attend study visits at the University of Wisconsin-Madison.

Brief summary: This study will be a longitudinal multiple-visit observational study, done to identify possible bioindicators of recovery and repair of motor corticospinal pathways which may be targeted by future interventions in infants with perinatal stroke.

65 participants will be recruited and complete 1 visit at time point 1 (0-2 months), and 2 visits at each timepoints 2-5 with windows of +- 4 weeks (3-6 months, 12 months, 18 months and 24 months). Visits will consist of Magnetic Resonance Imaging (MRI) assessment during the child's natural sleep, Transcranial Magnetic Stimulation (TMS), and Motor Behavioral Assessments.

Detailed description: Perinatal stroke has disabling consequences; 50-75% of individuals will develop life-long motor impairment, and 10-60% will also have cognitive deficits. These deficits lead to challenges in the school and home environments, with decreased likelihood of employment and independence and increased caregiver burden. Additionally, perinatal stroke is one of the primary causes of cerebral palsy (CP), a chronic and disabling neurological condition affecting motor function.

The first two years of life constitute a critical period of brain development and heightened neuroplasticity. There is now a consensus that, due to brain plasticity and rapid development, providing an early intervention may result in optimal recovery and lower costs of care. Unfortunately, researchers still have only limited understanding of how the brain develops after perinatal stroke and as a result CP diagnoses are typically not made until two years of age. There is an urgent need for very early diagnosis, prognosis and understanding of mechanisms in order to develop novel early interventions to improve outcomes in perinatal stroke with resultant CP.

Integrating study team's experience in studying and caring for this vulnerable infant stroke population, they propose to use non-invasive brain stimulation, neuroimaging, and behavioral assessments to analyze associations between development patterns, especially in the CST, and potential diagnosis of CP.

Specific aims of this study are:

* Aim 1. Map the presence and excitability of corticospinal pathways.
* Aim 2. Map the structural integrity and connectivity of corticospinal pathways.
* Aim 3. Compare motor outcomes from clinical behavioral assessments against corticospinal tract excitability and integrity.
* Aim 4. Identify the association between brain white-matter connectivity and general movements.
* Aim 5. Identify the association between corticospinal circuitry and general movements.

Protocol Amendment approved on 10/22/2021 removes TMS intervention and outcomes, adds a study time point at 0-2 months, and lowers the eligibility age to term.

Protocol Amendment approved on 12/21/2021 adds the TMS intervention back.

Eligibility criteria: Main Inclusion Criteria:

* Infants with corrected gestational age between term age and 24 months of age at study enrollment
* Radiologically-confirmed acute unilateral or bilateral brain lesions, including perinatal stroke, neonatal hemorrhagic or thrombotic stroke, involving the motor cortex and/or subcortical structures, and intracranial hemorrhage, involving the motor cortex and/or subcortical white matter, periventricular leukomalacia, and hypoxic-ischemic encephalopathy (HIE)
* English-speaking parent/legal guardian (able to provide consent)

Main Exclusion Criteria:

* Other neurologic disorders unrelated to perinatal stroke/brain bleed/HIE
* Metabolic disorders
* Disorders of Cellular Migration and Proliferation
* Acquired Traumatic Brain Injury

Primary outcomes:
measure: Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP)
timeFrame: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in Cortical excitability measured by intensity of motor threshold (MT)
timeFrame: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in Mean Fractional Anisotropy (FA) within the CST
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
timeFrame: 1 ±1 month
measure: Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
timeFrame: 3 ±1 months
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
timeFrame: 1 ±1 month
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
timeFrame: 3-6 months (one visit in this time frame)
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
timeFrame: 12±1 months
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
timeFrame: 18±1 months
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
timeFrame: 24±1 months
measure: Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scores
timeFrame: data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
timeFrame: 3-6 months (one visit in this time frame)
measure: Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
timeFrame: 12±1 months
measure: Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score
timeFrame: 18±1 months
measure: Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
timeFrame: 24±1 months
measure: Baby Observation of Selective Control AppRaisal (Baby OSCAR)
timeFrame: 1±1 month
measure: Baby Observation of Selective Control AppRaisal (Baby OSCAR)
timeFrame: 3-6 months (one visit in this time frame)
measure: Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Secondary outcomes:
measure: Change in blood pressure
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in heart rate
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in skin integrity reported as presence/absence of skin redness/rash
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in body temperature
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
measure: Change in respiration rate
timeFrame: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Bernadette Gillick, PhD, MSPT
role: PRINCIPAL_INVESTIGATOR
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