NCT05013736

Baby Brain Recovery Study

Perinatal Stroke: Longitudinal Assessment of Infant Brain Organization and Recovery Through Neuroexcitability, Neuroimaging and Motor Development

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 65 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 0 Years – 24 Months
• Healthy volunteers: Not accepted

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.

Conditions

• Perinatal Stroke

Interventions

Type	Name	Description
DEVICE	Magnetic Resonance Imaging	3 Tesla Discovery MR750 MRI scanner (GE Healthcare, Waukesha, WI) will be used to perform structural imaging, diffusion MRI, relaxometry and microstructural imaging. The exact scan length and parameters of each scan type (T1, T2, DWI) will be set for this study to optimize the quality of data and decrease the length of scanning session for each type of scan. All of the imaging methods have been previously implemented at UW-Madison. Each sequence will take approximately 5-10 minutes.
BEHAVIORAL	Behavioral Assessments	The behavioral assessments (GMA: General Movements Assessment; HINE: Hammersmith Infant Neurological Examination; Baby Observation of Selective Control AppRaisal (BabyOSCAR); Bayley-4 / Bayley Scales of Infant and Toddler Development 4th ed; Pediatric Evaluation of Disability Inventory -Computer Adaptive Test (PEDI-CAT)) are infant and age-specific and will be administered by trained pediatric occupational and physical therapists.
DEVICE	Non invasive Transcranial Magnetic Stimulation	TMS will be used to assess cortical excitability and circuitry (not as a neuromodulation intervention). Single-pulse TMS (Magstim 200², Magstim, UK) with a scalp surface coil will be used to assess how the brain is developing and how connected the tract is, between the brain and a target muscle on the arm. 10-20 TMS stimulation pulses will be delivered at a range of stimulation intensities (50-100%) increasing by 5% maximal stimulator output (MSO) at each stage. After this assessment, a brief assessment of peripheral nerve excitability will be performed. Peripheral stimulation will begin at 40% MSO. Stimulation intensity will be adjusted in increments of 5% until motor responses are evident on the EMG. Once motor responses are identified, 10 pulses will be delivered at the stimulation intensity that produced the response. In sum, around 150 stimulation pulses per hemisphere of brain stimulation and 22-60 pulses of peripheral stimulation are expected for TMS assessment of each infant.

Timeline

• Start date: 2022-07-26
• Primary completion: 2026-09-01
• Completion: 2026-09-01
• First posted: 2021-08-19
• Last updated: 2026-01-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study