Clinical Trial: Modulation of Brain Plasticity After Perinatal Stroke

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Modulation of Brain Plasticity After Perinatal Stroke: The PLASTIC CHAMPS Trial

Brief Summary:

Newborn stroke is the leading cause of a common type of cerebral palsy (CP) that affects thousands of Canadian children and families. Treatments for CP are generally ineffective, and have traditionally focused on the weak body rather than the injured brain. Understanding how the newborn brain responds to injuries like stroke (plasticity) carries the greatest potential for better treatments. We propose to study the ability of two interventions to modulate brain plasticity toward better function in children with stroke-induced CP. One is a rehabilitation method called constraint-induced movement therapy (CIMT), the other is a type of non-invasive brain stimulation called transcranial magnetic stimulation (TMS). TMS is safe and comfortable for children and we recently showed it could improve motor function in children with stroke.

We will perform a special study to test both treatments simultaneously. Children 7-18 years with stroke-induced CP will be recruited into the study from across Alberta. Each child will randomly receive either TMS, CIMT, both, or neither each day for two weeks while attending our new HemiKids Power Camp for motor learning. Improvements will be measured by trained therapists over 1 year. TMS will also measure brain plasticity, both initially and following treatment. Our lead investigator is an expert in both newborn stroke and TMS and has assembled an experienced team of accomplished collaborators to ensure the completion of this important work. This will be the largest study of children with CP examined in this manner. This will be the first clinical trial of non-invasive brain stimulation (TMS) in CP, the largest trial of CIMT (and the first exclusive to newborn stroke), and the first study allowing the direct comparison of two different therapies. In establishing the first dedicated pediatric TMS laboratory in Canada, we will be the first to measu

Detailed Summary:

Perinatal stroke is the leading cause of the most common term-born cerebral palsy: hemiplegic CP (HCP). With morbidity spanning all aspects of a child's life and lasting for decades, global impact is large. Mechanisms are poorly understood and prevention strategies remain elusive. Treatments are limited, leading to loss of hope in children and families that merits exploration of new interventions. Constraint-induced movement therapy (CIMT) may benefit but proper clinical trials are required. The investigators clinical-radiographic classifications have established perinatal stroke syndromes correlating with neurological outcome. Most common are: (1) arterial ischemic stroke of the middle cerebral artery (AIS-MCA) featuring cortical and subcortical damage acquired at birth and (2) periventricular venous infarction (PVI), a novel subcortical injury acquired in utero. These syndromes differ in the essential variables for plastic organization after perinatal injury: location and timing. In addition, recent animal and human studies suggest they may share a similar maladaptive plasticity whereby motor control of the weak side is "installed" in the non-lesioned hemisphere during development. Despite the ideal plasticity model such focal injury in a young brain provides, studies have been limited and suffer from small numbers of older patients with heterogeneous lesions. The value of studying plastic organization will be realized upon translation into meaningful patient benefits.

Transcranial magnetic stimulation (TMS) offers non-invasive measurement of the neurophysiological brain properties underlying neuroplasticity. Repetitive TMS (rTMS) may modulate such systems with therapeutic effect. the investigators recently demonstrated the ability of rTMS to improve motor function in children with chronic stroke. Advances in perinatal brain injury and neurodevelopment are, fo
Sponsor: University of Calgary

Current Primary Outcome:

  • Canadian Occupational Performance Measure (COPM). [ Time Frame: Completed 2 weeks or less before treatment day 1 ]
    The COPM is an individualized, family-centered tool designed to guide participants to identify self-perception of difficulties in self-care, productivity (i.e school) and leisure activities.
  • Canadian Occupational Performance Measure (COPM) [ Time Frame: Completed day 5 after treatment day 10 ]
    The COPM is an individualized, family-centered tool designed to guide participants to identify self-perception of difficulties in self-care, productivity (i.e school) and leisure activities.
  • Canadian Occupational Performance Measure (COPM) [ Time Frame: Completed 2 months after treatment day 10 ]
    The COPM is an individualized, family-centered tool designed to guide participants to identify self-perception of difficulties in self-care, productivity (i.e school) and leisure activities.
  • Canadian Occupational Performance Measure (COPM) [ Time Frame: Completed 6 months after treatment day 10 ]
    The COPM is an individualized, family-centered tool designed to guide participants to identify self-perception of difficulties in self-care, productivity (i.e school) and leisure activities.


Original Primary Outcome: Canadian Occupational Performance Measure (COPM). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]

The COPM is an individualized, family-centered tool designed to guide participants to identify self-perception of difficulties in self-care, productivity (i.e school) and leisure activities.


Current Secondary Outcome:

  • PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12) [ Time Frame: Completed 2 weeks or less before treatment day 1 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health. The PedsQL-CP is a condition specific health related quality of life instrument validated for child self-report (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participants. The PedsQL-CP includes scales of: daily activities, school activities, movement/balance, pain/hurt, fatigue, eating activities, and speech/communication.
  • PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12) [ Time Frame: Completed 5 days after treatment day 10 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health. The PedsQL-CP is a condition specific health related quality of life instrument validated for child self-report (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participants. The PedsQL-CP includes scales of: daily activities, school activities, movement/balance, pain/hurt, fatigue, eating activities, and speech/communication.
  • PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12) [ Time Frame: Completed 2 months after treatment day 10 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health. The PedsQL-CP is a condition specific health related quality of life instrument validated for child self-report (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participants. The PedsQL-CP includes scales of: daily activities, school activities, movement/balance, pain/hurt, fatigue, eating activities, and speech/communication.
  • PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12) [ Time Frame: Completed 6 months after treatment day 10 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health. The PedsQL-CP is a condition specific health related quality of life instrument validated for child self-report (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participants. The PedsQL-CP includes scales of: daily activities, school activities, movement/balance, pain/hurt, fatigue, eating activities, and speech/communication.
  • Pediatric Stroke Outcome Measure Short Neuro Exam Child Version (>2 years)(PSOM) [ Time Frame: Completed before treatment day 1 ]
    This is a validated outcome measure for perinatal and childhood stroke.
  • PedsQL Cerebral Palsy Module version 3.0 Parent Report for young child(ages 5-7), Parent Report for Child(ages 8-12), Parent report for teen(ages 8-12) [ Time Frame: Completed 2 weeks or less before treatment day 1 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health from a parents perspective. The PedsQL-CP is a condition specific health related quality of life instrument validated for parent-report of their child (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participant's parents.
  • PedsQL Cerebral Palsy Module version 3.0 Parent Report for young child(ages 5-7), Parent Report for Child(ages 8-12), Parent report for teen(ages 8-12) [ Time Frame: Completed day 5 after treatment day 10 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health from a parents perspective. The PedsQL-CP is a condition specific health related quality of life instrument validated for parent-report of their child (5-18yrs). Version of PedsQL-CP used is age specific and will be completed by all participant's parents.
  • PedsQL Cerebral Palsy Module version 3.0 Parent Report for young child(ages 5-7), Parent Report for Child(ages 8-12), Parent report for teen(ages 8-12) [ Time Frame: Completed 2 months after treatment day 10 ]
    This instrument assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health from a parents perspective. The PedsQL-CP is a condition specific health related quality of life instrument validated for parent-report of their child (5-18yrs). Version of PedsQL-CP used is age specific and wi

    Original Secondary Outcome:

    • Grip and pinch strength (GS, PS). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      Grip and pinch strength (GS, PS) are simple, quick measures of motor power), quantifiable with hand dynamometer that have been evaluated in children with HCP and employed most rTMS stroke and CIMT trials.
    • Assisting Hand Assessment (AHA). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      Assisting Hand Assessment (AHA) is a sensitive, reliable, and validated assessment of bimanual tasks (functional assistive role of the weak hand) in children with HCP. The AHA has excellent clinimetric properties for evaluating bimanual hand activities in HCP and pCIMT trials.
    • Melbourne Assessment of Unilateral Upper Limb Function (MAUULF). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      A validated, criterion-referenced functional measure designed to detect therapeutic clinical change in children with HCP. Testing in children with moderate CP demonstrates high intra and inter-rater reliabilities and construct validity. We have demonstrated the utility of the MAUULF in the only previous rTMS trial in children 7-20 years with stroke-induced hemiparesis.
    • ABILHAND-KIDS questionnaire. [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      Measures manual ability in children (ages 6-15) with CP as perceived by the parents.
    • Pediatric Motor Activity Log (PMAL). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      Commonly used in pCIMT studies with documented test-retest stability and sensitivity to change.A recent reversion developed using Rasch modeling has improved psychometric properties Completed independently by parents
    • Quality of Life (QoL). [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      The CP QoL-Child is a psychometrically sound condition specific instrument for children with CP (4-12yrs). It assesses domains of social/emotional well-being/acceptance, functioning, participation and physical health, access to services, pain and feelings about disability, and family health. The PedsQL-CP is a condition specific health related QoL instrument validated for child self-report (5-18yrs) and will be completed by all participants. The PedsQL-CP includes scales of: daily activities, school activities, movement/balance, pain/hurt, fatigue, eating activities, and speech/communication.
    • Pediatric Stroke Outcome Measure (PSOM) [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      This is a validated outcome measure for perinatal and childhood stroke. Assessment will include a standardized video-taped neurological examination with quantification of mirror movements.
    • SHUEE (Shriners Hospital Upper Extremity Evaluation) [ Time Frame: <2 weeks before treatment day 1; 5 days, 2 months and 6 months post treatment ]
      The Shriners Hospital for Children Upper Extremity Evaluation (SHUEE) is a video-based tool for the assessment of upper extremity function in children with hemiplegic cerebral palsy. This tool includes spontaneous functional analysis and dynamic positional analysis and assesses the ability to perform grasp and release.


    Information By: University of Calgary

    Dates:
    Date Received: August 20, 2010
    Date Started: August 2010
    Date Completion: March 2014
    Last Updated: October 21, 2013
    Last Verified: October 2013