Clinical trial NCT04902521: Use of Transcranial Magnetic Stimulation and Constraint Induced Movement Therapy in Pediatric Unilateral Cerebral Palsy
Official title: Concurrent Use of Transcranial Magnetic Stimulation and Constraint Induced Movement Therapy in Children With Unilateral Cerebral Palsy: A Feasibility Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebral Palsy
Keywords: cerebral palsy
constrain induced muscle therapy
Transcranial magnetic stimulation
Lead sponsor: University of Manitoba
Sponsor class: OTHER
First posted: 2021-05-26
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cerebral Palsy (CP) is the most common cause of childhood physical disability. Early CP diagnosis and intervention are crucial to improving outcomes in these patients. Constraint-induced movement therapy (CIMT) has become a standard therapeutic intervention for children with unilateral CP. CIMT utilizes restraining of the unaffected upper limb to stimulate the use of the paretic upper limb enhancing neuroplasticity in the affected cerebral hemisphere.

Transcranial magnetic stimulation (TMS) is a safe non-invasive technique that stimulates the brain using repetitive magnetic pulses to enhance neuroplasticity. TMS has been shown to improve symptoms of children with neurodevelopmental disorders such as CP. It is predicted that a combined therapy that uses CIMT and TMS is could improve mobility in children with unilateral CP.

To determine if combined therapy is beneficial to children with CP and if use of this therapy is feasible for families, the investigators would like to conducted a feasibility trial. In this trial the investigators will enrol 10 children who have unilateral CP, the participants will either receive:

1. CIMT and TMS or;
2. CIMT and fake TMS, fake TMS consist of a child sitting near the TMS machine but not receiving any TMS.

The aim of this project is to determine if it is feasible to conduct a large randomized control trial to compare the effects of combined CIMT and TMS versus CIMT and fake TMS.The investigators also hope that by conducting this trial they can identify any benefits that the addition of TMS may have in children with CP.

Detailed description: Cerebral Palsy (CP) is the most common cause of childhood physical disability. Early CP diagnosis and intervention are crucial in optimizing neuroplasticity and improving outcomes. One such intervention is constraint-induced movement therapy (CIMT), a therapeutic approach used in children with unilateral CP. CIMT utilizes restraining of the unaffected upper limb to stimulate the use of the paretic upper limb enhancing neuroplasticity in the affected cerebral hemisphere.CIMT is more effective than other rehabilitation approaches in improving upper limb function and has become a standard therapeutic intervention for children with unilateral CP.

Repetitive transcranial magnetic stimulation (TMS) is a safe non-invasive technique that stimulates the brain using repetitive magnetic pulses to enhance neuroplasticity. TMS has been shown to produce lasting modulation of cortical activity and improve clinical symptoms of children with neurodevelopmental disorders including CP.

A recent Canadian study, the PLASTIC Champs trial, demonstrated that combining TMS and CIMT for children with unilateral CP secondary to perinatal stroke produced greater improvements in upper limb function when compared to CIMT or TMS alone. Though promising, there are three features of the Plastic Champs trial that could limit its generalizability. First, it took place in a very special, intensive setting of daily CIMT/TMS during a 14-day camp. Second is the single cause of CP studied. And finally, it included only school-age children. To date, no research study has evaluated if findings from the PLASTIC Champs trial could be replicated when utilizing the combination of CIMT and TMS in a regular clinical environment, and among younger children.

A feasibility study is an appropriate first step towards our plan of performing a definitive RCT on the topic.

In this trial the investigators will enrol 10 children who have unilateral CP, they will either receive:

1. CIMT and TMS or;
2. CIMT and fake TMS, fake TMS consist of a child sitting near the TMS machine but not receiving any TMS.

The Investigators seek to evaluate whether, in younger children, the addition of TMS to the more commonly used, intermittent outpatient regimen of CIMT improves the motor outcomes of the upper limb.

Eligibility criteria: Inclusion Criteria:

* diagnosis of unilateral spastic CP
* assessed as Gross Motor Function Classification System level I to III
* assessed as Manual Ability Classification System level II to level IV

Exclusion Criteria:

* have received CIMT in the last 6 month
* do not have neuroimaging studies to confirm clinical diagnosis of CP
* severe impairments limiting their ability to participate

Primary outcomes:
measure: Evaluation of Participant recruitment
timeFrame: 5 Months
measure: Evaluation of Participant retention during trial
timeFrame: 5 Months
measure: Incidence of Treatment-Emergent Adverse Events as assessed by Parental Reports
timeFrame: 5 Months
measure: Effectiveness of the transcrainial magnetic stimulation blinding process on patients and therapist
timeFrame: 5 months
measure: Evaluation of treatment intervention by parental guardians
timeFrame: 3 months
measure: Estimation of intervention costs
timeFrame: 5 months
Secondary outcomes:
measure: Assessment of mobility using Small Kids-AHA
timeFrame: 5 months
measure: Assessment of mobility using the Canadian Occupational Performance Measure (COPM)
timeFrame: 5 months
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: SSCY/RCC
state: Manitoba
Study officials:
References:
citation: Rosenbaum P, Paneth N, Leviton A, Goldstein M, Bax M, Damiano D, Dan B, Jacobsson B. A report: the definition and classification of cerebral palsy April 2006. Dev Med Child Neurol Suppl. 2007 Feb;109:8-14.
citation: Novak I, Morgan C, Adde L, Blackman J, Boyd RN, Brunstrom-Hernandez J, Cioni G, Damiano D, Darrah J, Eliasson AC, de Vries LS, Einspieler C, Fahey M, Fehlings D, Ferriero DM, Fetters L, Fiori S, Forssberg H, Gordon AM, Greaves S, Guzzetta A, Hadders-Algra M, Harbourne R, Kakooza-Mwesige A, Karlsson P, Krumlinde-Sundholm L, Latal B, Loughran-Fowlds A, Maitre N, McIntyre S, Noritz G, Pennington L, Romeo DM, Shepherd R, Spittle AJ, Thornton M, Valentine J, Walker K, White R, Badawi N. Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment. JAMA Pediatr. 2017 Sep 1;171(9):897-907. doi: 10.1001/jamapediatrics.2017.1689.
citation: Gordon AM. To constrain or not to constrain, and other stories of intensive upper extremity training for children with unilateral cerebral palsy. Dev Med Child Neurol. 2011 Sep;53 Suppl 4:56-61. doi: 10.1111/j.1469-8749.2011.04066.x.
citation: Uswatte G, Taub E. Constraint-induced movement therapy: a method for harnessing neuroplasticity to treat motor disorders. Prog Brain Res. 2013;207:379-401. doi: 10.1016/B978-0-444-63327-9.00015-1.
citation: Chen YP, Pope S, Tyler D, Warren GL. Effectiveness of constraint-induced movement therapy on upper-extremity function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials. Clin Rehabil. 2014 Oct;28(10):939-53. doi: 10.1177/0269215514544982. Epub 2014 Aug 14.
citation: Sakzewski L, Ziviani J, Boyd RN. Efficacy of upper limb therapies for unilateral cerebral palsy: a meta-analysis. Pediatrics. 2014 Jan;133(1):e175-204. doi: 10.1542/peds.2013-0675. Epub 2013 Dec 23.
citation: Eliasson AC, Holmefur M. The influence of early modified constraint-induced movement therapy training on the longitudinal development of hand function in children with unilateral cerebral palsy. Dev Med Child Neurol. 2015 Jan;57(1):89-94. doi: 10.1111/dmcn.12589. Epub 2014 Sep 19.
citation: Masuda F, Nakajima S, Miyazaki T, Tarumi R, Ogyu K, Wada M, Tsugawa S, Croarkin PE, Mimura M, Noda Y. Clinical effectiveness of repetitive transcranial magnetic stimulation treatment in children and adolescents with neurodevelopmental disorders: A systematic review. Autism. 2019 Oct;23(7):1614-1629. doi: 10.1177/1362361318822502. Epub 2019 Jan 20.
citation: Kirton 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.