Baby Brain Recovery Study

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 0 years to 24 months
• All sexes
• No healthy volunteers
• Child

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

About this study

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

Conditions

Perinatal Stroke

Being tested

Magnetic Resonance Imaging, Behavioral Assessments, Non invasive Transcranial Magnetic Stimulation

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

Medical subject headings

Hypoxia-Ischemia, Brain, Brain Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Magnetic Resonance ImagingDevice

  Also called MRI

  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 AssessmentsBehavioural

  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.

• Non invasive Transcranial Magnetic StimulationDevice

  Also called TMS

  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.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP)

   Motor evoked potentials (MEPs) are the electrical signals recorded from the descending motor pathways or from muscles following stimulation of motor pathways within the brain.

   Responses from TMS pulses will be measured by recording muscle activity, referred to as motor evoked potentials (MEP).

   Measured: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

2. Change in Cortical excitability measured by intensity of motor threshold (MT)

   The MT is the minimum stimulation intensity that will elicit a consistent MEP of a pre-determined amplitude. MT and MEP are the common measures of TMS-induced excitability. Together, these measures provide information about the brain's excitability, associated with synaptic activity.

   Measured: 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

3. Change in Mean Fractional Anisotropy (FA) within the CST

   Mean Fractional Anisotropy (FA) within the CST will be used to study structural connectivity. It is a dimensionless index between 0 and 1. (0 equals no anisotropy; greater anisotropy is indicated by higher FA values approaching the maximum of 1).

   N=10 infants aged 0-2 months (first timepoint) will participate in MRI scans

   Measured: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

4. Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale

   The General Movements Assessment is used to identify absent or abnormal general movements. GMA requires 5-10 minutes video taping when infants are placed in spine position for scoring.

   "Absence or abnormal movements" will be reported as "Y".

   Measured: 1 ±1 month

5. Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale

   The General Movements Assessment is used to identify absent or abnormal general movements. GMA requires 5-10 minutes video taping when infants are placed in spine position for scoring.

   "Absence or abnormal movements" will be reported as "Y".

   Measured: 3 ±1 months

6. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score

   The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.

   The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are <57 at 3 months and <73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

   Measured: 1 ±1 month

7. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score

   The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.

   The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are <57 at 3 months and <73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

   Measured: 3-6 months (one visit in this time frame)

8. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score

   The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.

   The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are <57 at 3 months and <73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

   Measured: 12±1 months

9. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score

   The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.

   The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are <57 at 3 months and <73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

   Measured: 18±1 months

10. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score

    The HINE includes three sections, the Neurological Examination, the Development of Motor Functions and the State of Behaviour. The first section evaluates cranial nerve, posture, movements, tone and reflexes. These items are not age-dependent. The second section evaluates head control, sitting, voluntary grasping, rolling, crawling and walking. The third section evaluates state of consciousness, emotional state and social orientation.

    The maximum score for any one item is a score of 3 and the minimum is a score of 0. A subscore can be given for each section and the overall global score can be calculated by summing up all 26 items (range: 0-78), with higher scores indicating better neurological performance. High-risk cutoff scores for cerebral palsy are <57 at 3 months and <73 at 6, 9, or 12 months. See Novak et al, 2017 linked in the reference section for context.

    Measured: 24±1 months

11. Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scores

    An asymmetry can also be recorded for each item, with one point maximum allotted per item, with a total score ranging from 0-26. Based on the literature regarding asymmetries, the cutoff score of >3 asymmetries will be used for recommendation of referral to early intervention service. See article by Fehlings, 2024 for additional context.

    Measured: data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

12. Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score

    Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

    Measured: 3-6 months (one visit in this time frame)

13. Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score

    Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

    Measured: 12±1 months

14. Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score

    Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

    Measured: 18±1 months

15. Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score

    Bayley-4 is a developmental test that measures cognitive, language, motor, and social-emotional domains of infants and young children between 1 and 42 months of age. A higher score generally corresponds with higher function.

    Measured: 24±1 months

16. Baby Observation of Selective Control AppRaisal (Baby OSCAR)

    Baby OSCAR assessments are scored from video recordings of infant movement. Each limb is scored separately, with scores ranging 0-7 per lower limb, and 0-9 per upper limb for a total score of 0-32. Higher scores indicate better selective motor control.

    Measured: 1±1 month

17. Baby Observation of Selective Control AppRaisal (Baby OSCAR)

    Baby OSCAR assessments are scored from video recordings of infant movement. Each limb is scored separately, with scores ranging 0-7 per lower limb, and 0-9 per upper limb for a total score of 0-32. Higher scores indicate better selective motor control.

    Measured: 3-6 months (one visit in this time frame)

18. Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)

    Patient/caregiver-reported outcome measure of functional abilities and performance in children with disabilities. Scores are displayed instantly after completion of an assessment. A Detailed Score Report and a Summary Score Report are available. Normative scores are provided as age percentiles and T scores are based on a child's chronological age and intended for use by clinicians so that they may interpret a particular child's functioning relative to others of the same age. Scaled scores provide a way to look at a child's current functional skills and progress in these skills over time. Scaled scores are especially helpful in documenting improvements in functional skills for children not expected to exhibit or regain normative levels of functioning.

    Measured: 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted19 Aug 2021
2. Study start26 Jul 2022
3. Primary completionJun 2027 (estimated)
4. Study completionJun 2027 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (23)Papers the sponsor has linked to this study.
• Other trials for Perinatal StrokeStudies 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.