Use of Transcranial Magnetic Stimulation and Constraint Induced Movement Therapy in Pediatric Unilateral Cerebral Palsy

Study Overview
=================
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: CIMT and TMS or; 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: CIMT and TMS or; 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.

Official Title
-----------------
Concurrent Use of Transcranial Magnetic Stimulation and Constraint Induced Movement Therapy in Children With Unilateral Cerebral Palsy: A Feasibility Study

Conditions
-----------------
Cerebral Palsy

Intervention / Treatment
-----------------
* Device: Transcranial magnetic stimulation
* Device: Sham Transcranial Magnetic stimulation


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Months
Maximum Age: 5 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial magnetic stimulation with constraint induced movement therapy<br>CIMT/TMS: Five participants will receive a one-hour weekly occupational therapy session of CIMT with 2-hours of daily home program for a total of 6 weeks; immediately prior to initiation of each CIMT session, participants will receive 20 minutes of TMS 1HZ. | Device: Transcranial magnetic stimulation<br>* 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<br>* Other names: TMS;|
| Sham Comparator: constraint induced movement therapy Sham transcrianial magnetic stimulation<br>(CIMT/sham TMS): Five participants will receive a one-hour weekly session of CIMT with 2-hours daily of home program for a total of 6 weeks; immediately prior to initiation of each CIMT session, participants will receive 20 minutes of sham TMS 1HZ. | Device: Sham Transcranial Magnetic stimulation<br>* Sham Transcranial Magnetic stimulation will be given to the control group. During the Sham procedure patients will sit near the TMS but will not receive any magnetic pulses.<br>* Other names: Sham TMS;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Participant recruitment | Participant recruitment: We will assess number of eligible children, reasons for ineligibility and non-participation. | 5 Months | 
| Evaluation of Participant retention during trial | We will assess and report the number of missing variables and number of patients with incomplete outcome measures. | 5 Months | 
| Incidence of Treatment-Emergent Adverse Events as assessed by Parental Reports | We will ask parents to report weekly on the presence of previously reported side effects including headaches, anxiety, dizziness, tingling, mood changes, difficulties with concentration, abnormal muscle contractions, nausea, stomach ache, fatigue and decreased hand function of either hand. For completeness we will also ask about presence of seizures (new onset or increase in existing seizures), although this side effect was not seen in previous safety studies. We will also assess number of times (and reasons) TMS session ended before the stipulated time and number of minutes lost. | 5 Months | 
| Effectiveness of the transcrainial magnetic stimulation blinding process on patients and therapist | TMS sham process and blinding of patients and therapist: At the end of the study we will ask parents/ occupational therapist assessing outcomes to report on possible group allocation of participant (could they identify if the participant received TMS or sham TMS?) | 5 months | 
| Evaluation of treatment intervention by parental guardians | Acceptability of treatment: Based on Gillick's work, at the end of the intervention (6 weeks) and 3 months post completion, we will ask parents to rate on a scale of 1 to 10 their satisfaction with the intervention, willingness to repeat the study, and likelihood of recommending the study to others. . - Participant research engagement: At the end of the study we will ask parents to rate their willingness to participate as a research-collaborator in a future large RCT study. | 3 months | 
| Estimation of intervention costs | This study will provide information needed to develop a budget for the future application. | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of mobility using Small Kids-AHA | We will assess differences between pre-to post intervention using the Small Kids- AHA scores among those undergoing CIMT+TMS vs. CIMT/sham TMS. Small Kids-AHA is a measure of bimanual performance and is rated on a scale or 0-100 (100 being high functionality). | 5 months | 
| Assessment of mobility using the Canadian Occupational Performance Measure (COPM) | We will assess differences between pre-to post intervention using the Canadian Occupational Performance Measure (COPM) scores among those undergoing CIMT+TMS vs. CIMT/sham TMS. Canadian Occupational Performance Measure is used to asses daily functioning and is scored on a 10 point scale (10 being high functionality). | 5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cerebral palsy, constrain induced muscle therapy, Transcranial magnetic stimulation