Pediatric Teleneuromodulation

Study Overview
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Brief Summary
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This study will explore using remotely monitored 'active' non-invasive brain stimulation in children with cerebral palsy. Participants will receive active non-invasive brain stimulation with synchronous safety monitoring and guided instruction with laboratory staff after appropriate training. Participants will be between 8-21 years old and have a diagnosis of hemiparetic cerebral palsy with a history of a perinatal stroke or brain bleed, and can expect to be in the study for 5 days.

Detailed Description
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Current exploratory single site open label unblinded trial, will assess the feasibility, tolerability, and safety of active tDCS in the home setting under caregiver, safety monitor and remote investigator supervision and direction. The study population will consist of 10 participants between ages 8 - 21 years and 365 days with hemiparetic cerebral palsy and a history of a brain bleed or stroke. An estimated 3.6 per 1,000 births in the United States are affected by stroke or brain bleeds which can lead to Cerebral Palsy (CP), a developmental disorder associated with motor impairment. While, the majority of rehabilitation approaches focus on behavioral repetition to improve gait and upper extremity function, these therapies can require extensive practice times and extent of recovery is variable. Thus, there is a need for novel strategies which can optimize rehabilitation outcomes for this population. Brain development during childhood is characterized by heighted neuroplastic potential stressing the importance for intervention methods that harness neuroplasticity. Accordingly, several therapies are theoretically based in mechanisms of motor learning and use-dependent plasticity. Non-invasive brain stimulation (NIBS), specifically transcranial direct current stimulation (tDCS), provides an approach for modulation of neuroplasticity that is safe, inexpensive, and portable. Furthermore, rehabilitation approaches combined with tDCS have shown promise to improve motor function recovery and quality of life after stroke in adults. Integrating the application of NIBS may allow for enhanced rehabilitation during the enhanced neuroplastic period of childhood and NIBS has demonstrated promising outcomes in increasing the rate and extent of recovery. The Pediatric Neuromodulation laboratory has shown that in children with CP the use of tDCS is safe, feasible, and successful at modifying motor performance when in combination with other physical therapy interventions. tDCS is not currently available to subjects without taking part in the study. In this study, investigators plan to administer tDCS in the remote setting during a synchronous zoom call with trained laboratory members. To ensure the device is safely used in the home setting only during designated times, in the presence of a trained safety monitor. The safety monitor will bring the device to the session, oversee the safety of its use, and take it back to the laboratory after the session is complete. This intervention has the potential to improve motor rehabilitation outcomes and can offer telehealth access, which may reduce treatment cost and improve access to limited access to clinic or hospital facilities. This study has the potential to set the foundation for larger clinical trials studies evaluating the efficacy of remote tDCS combined with rehabilitation interventions in children. Ultimately, this will contribute to a wider reach in improving quality of life across the lifespan in children with CP. On Day #1 there will be a practice stimulation montage setup assessment. Before their session, a GMFCS and pediatric cognition survey will be completed with the investigative team. All participants will be asked to view instructional videos on how to perform the procedures. Parent/child pairs will perform the assessment by walking through the steps with the guidance of the lab team member via videoconferencing. Efficiency and quality of setup data will be collected. A setup ease/comfort survey will be completed upon completion of the stimulation montage setup. Days 2-5 will consist of sham/active stimulation in the home setting under caregiver, safety monitor, and remote investigator supervision and direction. Status surveys inquiring well-being will be conducted before, during, and after stimulation as well as a Box and Blocks motor function tests. At any time the participant perceives discomfort while dosing to 1.5mA the investigators will adapt and modify the stimulation intensity. Protocol Amendment Approved 6/7/2023: addition of an optional 6 and 12 month study visit.

Official Title
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Remotely Monitored Transcranial Direct Current Stimulation in Children With Cerebral Palsy

Conditions
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Cerebral Palsy (CP)

Intervention / Treatment
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* Device: Soterix 1x1 tDCS LTE Stimulator Device Model 1401


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 8 years 0 days and 21 years 365 days Children who have hemiparetic cerebral palsy with a history of perinatal brain bleed/stroke Receptive language function to follow two-step commands Able to give informed assent along with the informed consent of the legal guardian. If the participant is 18-21 (with the capacity to consent), they must be able to give informed consent. Intentional about representing the sub-population of children with CP who experience intellectual disability (at least 2/10 participants with mild intellectual disabilities will be recruited) ≥ 10 degrees of active motion at the metacarpophalangeal joint Children who have had surgeries, which may influence motor function e.g.- tendon transfer, will be included, yet surgical history will be documented and included in any publication within a participant characteristics table. Exclusion Criteria: Inaccessibility to internet and a working computer/laptop/device. Implants Neoplasm Metabolic Disorders Epilepsy Seizure within two years preceding the study Acquired Traumatic Brain Injury Pregnancy Indwelling metal or incompatible medical devices Evidence of skin disease or skin abnormalities Botulinum toxin or Phenol block within [six-months] preceding the study Disorder of Cellular Migration and Proliferation To be eligible for the optional 6-month/12-month follow-up: participants must have previously participated in the primary study have access to a reliable internet connection and a functioning computer, laptop, or mobile device. If participants become pregnant after participating in primary study, they may participate in the 6- and 12-month follow up sessions

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Children diagnosed with stroke/brain bleed<br>Male and females aged 8 to 21 with established diagnosis of stroke/brain bleed who are US residents. | Device: Soterix 1x1 tDCS LTE Stimulator Device Model 1401<br>* Participants will receive 20 minutes of 1.5 mA (Milliampere) transcranial direct current stimulation (tDCS) via Soterix 1x1 tDCS LTE Stimulator Device Model 1401 with a bilateral M1 montage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Status/Safety Assessment | Before stimulation, the study team will work with the participant to fill out a status survey. In the survey, participants will be asked to report the severity of events they may experience. Since investigators are working with the pediatric population, the investigator makes the final decision on the likelihood of an event being related to the tDCS intervention versus the participant's environment. Serious adverse events, falling in the 3-5 categories (1-unrelated, 2- unlikely, 3- possible, 4- probable, 5- definite) will be considered related to the study. This determination is made with the parent/caregiver as witnesses and confirmed by the parent/caregiver. | Baseline - Day 1 | 
| Status/Safety Assessment | During stimulation, the study team will work with the participant to fill out a status survey. In the survey, participants will be asked to report the severity of events they may experience. Since investigators are working with the pediatric population, the investigator makes the final decision on the likelihood of an event being related to the tDCS intervention versus the participant's environment. Serious adverse events, falling in the 3-5 categories (1-unrelated, 2- unlikely, 3- possible, 4- probable, 5- definite) will be considered related to the study. This determination is made with the parent/caregiver as witnesses and confirmed by the parent/caregiver. | During stimulation on days 2-5 | 
| Status/Safety Assessment | After stimulation, the study team will work with the participant to fill out a status survey. In the survey, participants will be asked to report the severity of events they may experience. Since investigators are working with the pediatric population, the investigator makes the final decision on the likelihood of an event being related to the tDCS intervention versus the participant's environment. Serious adverse events, falling in the 3-5 categories (1-unrelated, 2- unlikely, 3- possible, 4- probable, 5- definite) will be considered related to the study. This determination is made with the parent/caregiver as witnesses and confirmed by the parent/caregiver. | Posttest on sessions 2, 3, 4, and 5 | 
| Change in tDCS headgear location | To evaluate the quality of device setup, we will measure any changes or movement of the headgear. To do this, we will mark the starting and ending location of the headgear and measure the distance between the two. It will be reported if the headgear moved in any participants and the average displacement. | Post sessions on day 1, 2, 3, 4 , and 5 | 
| Change in responses to ease of set up survey | To evaluate the feasibility of remotely monitored-tDCS, the difficulty of each step will be measured on an ordinal 3-point scale. A lower score will correspond with a lower difficulty setting. Average difficulty will be compared throughout all sessions to indicate any improvement throughout the study. | Post sessions on day 1, 2, 3, 4 , and 5 | 
| Change in responses to comfort survey | To evaluate the comfort of the device, participants will be asked a question on an ordinal 4-point scale. A lower score corresponds with a higher comfortability. | Post sessions on day 1, 2, 3, 4 , and 5, optional 6 month follow up, optional 12 month follow up | 
| Medical Record Review at 6 months | To assess medical status and the potential for new onset seizures, development of epilepsy, changes in motor function, and development of long-lasting symptons since participation in the primary study. | Optional 6 month follow up | 
| Medical Record Review at 12 months | To assess medical status and the potential for new onset seizures, development of epilepsy, changes in motor function, and development of long-lasting symptons since participation in the primary study. | Optional 12 month follow up | 
| Change in tDCS Subject Report of Symptoms Questionnaire | Summary table of symptoms participant has experienced since the primary study. | optional 6 and 12 month follow up | 
| Change in Qualitative tDCS Tolerance Survey | Qualitative analysis to compare the participants feedback regarding the tDCS. | optional 6 and 12 month follow up | 
| Change in Gross Motor Function Classification System | The gross motor function of children and young people with cerebral palsy is categorized into 5 different levels: Level 1 is the most independent movement (child can run and jump) to Level 5, the most dependent (transported in a manual wheelchair, for example) | baseline, optional 6 and 12 month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time to complete montage setup | To evaluate speed of device setup, time to complete montage set up will be measured. On the REDCap (Research Electronic Data Capture) survey, the researcher will click a now button that records the time to seconds at the beginning and end of montage set up. The lower time corresponds to ease in montage set up. | Pre-stimulation on day 1, 2, 3, 4 and 5 | 
| Change in contact quality (CQ) | SMARTscan™ contact quality is reported by the device throughout the stimulation and reflects quality of the stimulation delivery. Lower contact quality indicates the stimulation isn't being properly delivered. Changes in stimulation quality over the three active sessions using a Friedman test (non-parametric test for repeated measures) will be determined. Tests with a p-value of <0.05 will be considered significant. | Post stimulation on day 1, 2, 3, 4 and 5 | 
| Change in Box and Blocks assessment score | To evaluate the potential change in motor function, the Box and Blocks score will be measured before and after each active session. Motor function is not hypothesized to change due to the limited trials of active tDCS. | Post sessions on day 2, 3, 4 , and 5, optional 6 month follow up, optional 12 month follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children with cerebral palsy, Remote transcranial direct current stimulation (tDCS), Non-invasive brain stimulation (NIBS)