Modulation of Brain Plasticity After Perinatal Stroke
PLASTIC CHAMPS
1 other identifier
interventional
64
1 country
1
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 measure plasticity changes in newborn stroke, advancing new treatments of this previously untreatable and disabling disease. Patient recruitment is currently underway at Alberta Children's Hospital. Application is currently underway to expand recruitment to Northern Alberta through the Glenrose Rehabilitation Hospital and Stollery Children's Hospital, to enable patients from Northern Alberta greater opportunity to participate as subjects in this study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 stroke
Started Aug 2010
Typical duration for phase_2 stroke
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2010
CompletedFirst Submitted
Initial submission to the registry
August 20, 2010
CompletedFirst Posted
Study publicly available on registry
August 26, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2014
CompletedOctober 23, 2013
October 1, 2013
3.5 years
August 20, 2010
October 21, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Canadian Occupational Performance Measure (COPM).
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.
Completed 2 weeks or less before treatment day 1
Canadian Occupational Performance Measure (COPM)
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.
Completed day 5 after treatment day 10
Canadian Occupational Performance Measure (COPM)
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.
Completed 2 months after treatment day 10
Canadian Occupational Performance Measure (COPM)
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.
Completed 6 months after treatment day 10
Secondary Outcomes (47)
PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12)
Completed 2 weeks or less before treatment day 1
PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12)
Completed 5 days after treatment day 10
PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12)
Completed 2 months after treatment day 10
PedsQL Cerebral Palsy Module version 3.0 Young child report (ages 5-7), Child report (ages 8-12), Teen report (ages 8-12)
Completed 6 months after treatment day 10
Pediatric Stroke Outcome Measure Short Neuro Exam Child Version (>2 years)(PSOM)
Completed before treatment day 1
- +42 more secondary outcomes
Study Arms (4)
rTMS and CIMT
EXPERIMENTALThis group will receive both rTMS and CIMT.
rTMS and no CIMT
EXPERIMENTALThis group will receive rTMS only.
Sham and CIMT
EXPERIMENTALThis group will receive CIMT and sham rTMS.
Sham and no CIMT
NO INTERVENTIONThis group will receive sham rTMS and no CIMT.
Interventions
TMS can affect discrete functional ares of motor cortex offering non-invasive, painless mapping and modulation of motor systems. Inhibitory rTMS (1Hz)has been shown to safely lower motor cortex excitability in normal patients as well as adult and pediatric stroke patients. Dose is 20 minutes per day (1200 stimulations) x 10 days administered over the non-lesioned M1.
CIMT uses gentle restraint of the fully functional upper extremity to promote functional gains in the affected upper extremity. CIMT is well established to be safe and is likely effective in children with hemiplegic cerebral palsy, many of whom have perinatal stroke as studied here. A custom-fitted, bivalved cast is applied and worn for \>90% of waking hours for the 2 weeks of active treatment according to protocol with daily assessments for comfort.
Eligibility Criteria
You may qualify if:
- Symptomatic hemiplegic CP with impairment(s) of the upper extremity including the hand (Pediatric Stroke Outcome Measure motor \>0.5; AND Manual Ability Classification System I, II,III, or IV; AND both child and parent perceive functional limitations (able to identify personally meaningful deficits in function).
- MRI confirmed AIS-MCA or PVI (neuroradiological syndrome classified by two blinded, experienced investigators according to previously validated methods)
- Age at enrollment: 6-18 years
- Resident in province of Alberta for period of study
- Informed consent/assent
You may not qualify if:
- Multifocal perinatal stroke or other brain injury/abnormality
- Severe hemiparesis (no voluntary contraction in paretic hand, MACS level V)
- Intellectual disability causing an inability to comply with study protocol
- Unstable epilepsy (\>1 seizure/month or \>2 medication changes (dose or agent) in the last 6 months or history of recurrent status epilepticus)
- Any TMS contraindication including implanted electronic devices
- Botulinum toxin A injection in the affected upper extremity within the preceding 6 months
- Orthopedic surgery in the affected upper extremity in the previous 12 months
- Unwilling to delay any new therapeutic rehabilitational intervention directed towards upper limb function (aside from study home program) for the 6 month duration of the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Calgarylead
- Heart and Stroke Foundation of Canadacollaborator
- University of Albertacollaborator
Study Sites (1)
Alberta Childrens Hospital
Calgary, Alberta, T3B 6A8, Canada
Related Publications (9)
Kirton A, Shroff M, Pontigon AM, deVeber G. Risk factors and presentations of periventricular venous infarction vs arterial presumed perinatal ischemic stroke. Arch Neurol. 2010 Jul;67(7):842-8. doi: 10.1001/archneurol.2010.140.
PMID: 20625091BACKGROUNDKirton A, Deveber G, Gunraj C, Chen R. Cortical excitability and interhemispheric inhibition after subcortical pediatric stroke: plastic organization and effects of rTMS. Clin Neurophysiol. 2010 Nov;121(11):1922-9. doi: 10.1016/j.clinph.2010.04.021.
PMID: 20537584BACKGROUNDKirton A, Wei X. Teaching neuroimages: confirmation of prenatal periventricular venous infarction with susceptibility-weighted MRI. Neurology. 2010 Mar 23;74(12):e48. doi: 10.1212/WNL.0b013e3181d5a47a. No abstract available.
PMID: 20308675BACKGROUNDKirton A, deVeber G. Advances in perinatal ischemic stroke. Pediatr Neurol. 2009 Mar;40(3):205-14. doi: 10.1016/j.pediatrneurol.2008.09.018.
PMID: 19218034BACKGROUNDKirton A, Chen R, Friefeld S, Gunraj C, Pontigon AM, Deveber G. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 2008 Jun;7(6):507-13. doi: 10.1016/S1474-4422(08)70096-6. Epub 2008 May 1.
PMID: 18455961BACKGROUNDKirton A, Deveber G, Pontigon AM, Macgregor D, Shroff M. Presumed perinatal ischemic stroke: vascular classification predicts outcomes. Ann Neurol. 2008 Apr;63(4):436-43. doi: 10.1002/ana.21334.
PMID: 18306227BACKGROUNDKirton A, Westmacott R, deVeber G. Pediatric stroke: rehabilitation of focal injury in the developing brain. NeuroRehabilitation. 2007;22(5):371-82.
PMID: 18162700BACKGROUNDRaju TN, Nelson KB, Ferriero D, Lynch JK; NICHD-NINDS Perinatal Stroke Workshop Participants. Ischemic perinatal stroke: summary of a workshop sponsored by the National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Pediatrics. 2007 Sep;120(3):609-16. doi: 10.1542/peds.2007-0336.
PMID: 17766535BACKGROUNDKirton A, Andersen J, Herrero M, Nettel-Aguirre A, Carsolio L, Damji O, Keess J, Mineyko A, Hodge J, Hill MD. Brain stimulation and constraint for perinatal stroke hemiparesis: The PLASTIC CHAMPS Trial. Neurology. 2016 May 3;86(18):1659-67. doi: 10.1212/WNL.0000000000002646. Epub 2016 Mar 30.
PMID: 27029628DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Adam Kirton, MD MSc FRCPC
University of Calgary
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Pediatric Neurologist
Study Record Dates
First Submitted
August 20, 2010
First Posted
August 26, 2010
Study Start
August 1, 2010
Primary Completion
February 1, 2014
Study Completion
March 1, 2014
Last Updated
October 23, 2013
Record last verified: 2013-10