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围产期中风:婴儿期大脑重组

2026年9月15日 更新者:University of Wisconsin, Madison

围产期中风:通过神经兴奋性、神经影像学和运动发育对婴儿大脑组织和恢复进行纵向评估

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.

研究概览

详细说明

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.

研究类型

观察性的

注册 (估计的)

65

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习联系方式

  • 姓名:Bernadette Gillick, PhD, MSPT
  • 电话号码:608-262-3079
  • 邮箱:bgillick@wisc.edu

学习地点

    • Wisconsin
      • Madison、Wisconsin、美国、53705
        • 招聘中
        • University of Wisconsin School of Medicine and Public Health

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

1秒 至 2年 (孩子)

接受健康志愿者

不

有资格学习的性别

全部

取样方法

非概率样本

研究人群

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.

描述

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

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 观测模型:COHORT
  • 时间观点:PROSPECTIVE

队列和干预

团体/队列
干预/治疗
Infants

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 able to attend study visits at the University of Wisconsin-Madison.

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.

其他名称:
  • 核磁共振

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.

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.

其他名称:
  • 经颅磁刺激

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Change in Cortical excitability measured as presence/absence of motor evoked potentials (MEP)
大体时间:3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

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).

3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in Cortical excitability measured by intensity of motor threshold (MT)
大体时间:3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

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.

3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Change in Mean Fractional Anisotropy (FA) within the CST
大体时间:1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

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

1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
大体时间:1 ±1 month

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".

1 ±1 month
Behavioral assessments: General Movements Assessment (GMA) reported on binary (Y/N) scale
大体时间:3 ±1 months

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".

3 ±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
大体时间:1 ±1 month

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.

1 ±1 month
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
大体时间:3-6 months (one visit in this time frame)

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.

3-6 months (one visit in this time frame)
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
大体时间:12±1 months

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.

12±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
大体时间:18±1 months

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.

18±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) global score
大体时间:24±1 months

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.

24±1 months
Behavioral assessments: Hammersmith Infant Neurological Examination (HINE) Asymmetry Scores
大体时间:data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

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.

data collected at 1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
大体时间:3-6 months (one visit in this time frame)

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.

3-6 months (one visit in this time frame)
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
大体时间:12±1 months

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.

12±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-IV) score
大体时间:18±1 months

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.

18±1 months
Behavioral assessments: Bayley Scales of Infant and Toddler Development Test, 4th edition (Bayley-4) score
大体时间:24±1 months

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.

24±1 months
Baby Observation of Selective Control AppRaisal (Baby OSCAR)
大体时间:1±1 month

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.

1±1 month
Baby Observation of Selective Control AppRaisal (Baby OSCAR)
大体时间:3-6 months (one visit in this time frame)

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.

3-6 months (one visit in this time frame)
Change in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT)
大体时间:1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

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.

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

次要结果测量

结果测量
措施说明
大体时间
血压变化
大体时间:1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
心率变化
大体时间:1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
皮肤完整性的变化报告为存在/不存在皮肤发红/皮疹
大体时间:1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
体温变化
大体时间:1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
1±1个月、3-6个月(在此时间范围内就诊一次)、12±1个月、18±1个月、24±1个月
Change in respiration rate
大体时间:1 ±1 month, 3-6 months (one visit in this time frame), 12±1 months, 18±1 months, 24±1 months

Respiration rate will be measured as breaths/minute.

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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:Bernadette Gillick, PhD, MSPT、University of Wisconsin, Madison

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年7月26日

初级完成 (估计的)

2027年6月1日

研究完成 (估计的)

2027年6月1日

研究注册日期

首次提交

2021年8月13日

首先提交符合 QC 标准的

2021年8月13日

首次发布 (实际的)

2021年8月19日

研究记录更新

最后更新发布 (实际的)

2026年9月18日

上次提交的符合 QC 标准的更新

2026年9月15日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

Individual participant data collected during the trial will be shared after deidentification.

IPD 共享时间框架

Beginning 3 months after publication of primary outcomes, and ending 5 years after that date

IPD 共享访问标准

Data will be shared with the researchers whose proposed use of the data is for independent verification of study outcomes or to conduct subsequent clinical research. Data sharing will be approved by an independent review committee identified for this purpose.

Proposals should be directed to bgillick@wisc.edu. If approved after review by regulatory counsel, requestors will enter into a formal data sharing agreement. Data will be shared via encrypted single-user file transmission protocol.

IPD 共享支持信息类型

  • 研究方案
  • 树液

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

是的

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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