HD-tDCs to Improve Upper Extremity Function in Patients With Acute Middle Cerebral Artery Stroke

Study Overview
=================
Brief Summary
-----------------
To determine if using targeted high definition transcranial direct current stimulation can improve upper extremity motor function in patients with subacute middle cerebral artery (MCA) stroke.

Detailed Description
-----------------
Current research suggests there may be potential benefit using high definition transcranial direct current stimulation in patients with upper extremity hemiparesis secondary to an ischemic stroke. The intervention has effects on the damaged neurons within the person's brain after stroke possibly amplifying the body's own healing process. These data are compelling but not always statistically significant, which could be due to several reasons. One is the lack of a definitive protocol involving timing of the intervention relative to therapy, lead placement, an unclear dose-response relationship, and variable conductance of tissue and skull thickness. Hummel et al (2008) suggested that stimulation during or before intensive therapy yielded improved motor function or reaction time than when no therapy was given around the stimulation. Several other review articles and studies suggest using both high definition tDCS, which increases the focality of the current, and/or using neurotargeting software that uses the patient's own CT/MRI in the computation of the electrical montage can create a more personalized tDCS regimen.7,11,12 This study plans to do both. The Soterix MxN neuromodulation system has been used in multiple studies and has a targeting system that would help ensure both ideal current, more focal stimulation and optimal lead placements is essential as according to Datta et al (2011). Lesions within the brain may alter the flow of current through that area. The software system, HD-Targets, will be used that takes the patient's own MRI to account for variabilities in skull thickness, lesion size/location/composition, fluid density, and cerebrospinal fluid presence. These variabilities are used in the computer algorithm that simulates current flow through that specific participant's brain to get to the desired target area with the least amount of current and decreased stimulation of undesired areas. The investigators will examine these patients before and after treatment and compare the two groups, treatment group and sham group, after they receive 10 sessions of 20minutes along with their regular course of physical, occupational, or speech therapy over the course of their inpatient rehab stay. Subjects will be given high definition transcranial direct current stimulation (tDCS) via a Soterix MxN HD-tDCS stimulator. This device is for investigational use only at this time and is not FDA approved. However, it has been used in several multicenter and randomized control trials that are detailed below in Appendix 1. The patient's MRi will be sent out to Soterix where they will manually input the variations in skull thickness, fluid density, lesion size, cerebrospinal fluid, and gray/white matter variabilities. They will then run the algorithm with HD-Targets, sophisticated current simulating software, to obtain optimal electrode placement to target the primary motor cortex (M1 area), the region of the brain that is responsible for movement, of each individual patient. Another issue with tDCs is maintaining optimal connections between the patient's scalp and the electrodes. Sotetrix HD-tDCs uses SmartScan™ to assure proper lead contact with initial set-up to adjust electrodes and head-gear for optimal fit. During stimulation, SmartScan™ provides a constant indication of electrode quality and can be monitored during adjustments to assure continuous lead contact.

Official Title
-----------------
Pilot Study Using Targeted High Definition Transcranial Direct Current Stimulation to Promote Upper Extremity Motor Function in Patients With Subacute Middle Cerebral Artery (MCA) Stroke

Conditions
-----------------
Middle Cerebral Artery Stroke

Intervention / Treatment
-----------------
* Device: Soterix MxN Neuromodulation device
* Device: Sham Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18-90 years old Diagnosed with middle cerebral artery ischemic stroke Upper extremity movement deficits Cardiorespiratory function is stable Admitted to acute inpatient rehabilitation Intact corticospinal tract Exclusion Criteria: Previous stroke Pre-stoke weakness or disability in the paretic arm Severe neglect Acute exacerbation of heart failure or COPD Severe aphasia Decisional Impairment Pregnant or nursing women Prisoner Skin disorder or wound of scalp Seizure disorder

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 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
Interventional Model Description: Pilot prospective double blinded randomized controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Treatment with 'Soterix MxN Neuromodulation device (high definition transcranial direct current stimulator) using HD-Targets for optimal neural targeting will be provided to participants and will include 20 minutes of stimulation coupled with conventional OT treatment during and after the intervention. There will be a total of 10 sessions over about a 2 week period. | Device: Soterix MxN Neuromodulation device<br>* Up to 2 mA stimulation to primary motor cortex for 10 sessions at 20min per session<br>|
| Sham Comparator: Sham group<br>Sham stimulation will consist of using the devices auto-sham feature. The exact same setup/device will be used during both groups. This is considered a control for the experiment. Both groups will receive similar physical occupational and speech therapy | Device: Sham Stimulation<br>* Uses slight stimulation initially then turns of and provides no stimulation after a few seconds.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Fugl-Meyer upper extremity assessment | It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. It measures performances on motor function of the upper extremity. Range is from 0-66 with 66 being totally normal in all assessments. Each Sub score for each category ranges from 0-2 with 0 being not able to finish and 2 meaning function is normal in this category. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Wolf Motor Function Test | Quantifies upper extremity (UE) motor ability through timed and functional tasks. Thus, it measures how well a task can be performed by the subject, and the patient is given a score from 0-6. Zero being did not perform, and six being normal. The changes in performance can be compared over time to assess their progress. Each task is subscaled from 0-6 with 6 being indepednetly performed and 0 being unable to perform or needs to be performed by someone else for the patient. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Change in the Functional Independence Measure | A uniform system of measurement for disability based on the International Classification of Impairment, Disabilities and Handicaps for use in the medical system in the United States. It is a measure of a person's physical, psychological, and social functions to assess their level of disability. It is a scale from 18-126 with a score of 126 being completely normal or independent in all of the tasks. 17 tasks in total: 6 are functional tasks, 2 measure strength, and 9 analyze movement quality or efficiency. Each task is subscored from 1-7 with 7 being completely independent completing a task and 1 meaning the person is fully dependent on someone completing that task for them. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Change in the Action Research Arm Test | Evaluative measure to assess specific changes in limb function among individuals who sustained cortical damage resulting in hemiplegia (Lyle, 1981). This measures 19 items covering four domains of upper extremity movement: grasp, grip, pinch, and gross motor. Score ranges from 0-57 with 57 being normal function in all domains. Each task has a subscore of 0-3 with 0 being unable to perform movement and 3 being normal function. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Kinematic measurements with Kinereach system: measurement of change arm speed | Developed by Robert Sainburg. The machine is able to measure how fast a patient's arm is able to move through space. Speed would be quantified as the peak and/or average tangential velocity of the hand during self-paced reaching movements. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Kinematic measurements with Kinereach system: measurement of change in arm smoothness | Developed by Robert Sainburg. The machine is able to measure how smooth a patient is able to move their arm through space. Smoothness is measured as mean squared Jerk: This is quantified as the third derivative of displacement (jerk) squared and averaged over time. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Kinematic measurements with Kinereach system: measurement of change in arm range of motion | Developed by Robert Sainburg. The machine is able to measure range of motion that would be quantified as the largest 2D area encircled by the hand, when asked to make the biggest circle possible. . | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Change in National institute of Health Stroke Scale | 15-item impairment scale, intended to evaluate neurologic outcome and degree of recovery for patients with stroke. Range of scores from 0-42 with zero being no symptoms and 42 being severely impaired. It is a way to quantify stroke severity with measures for the typical stroke symptoms including level on consciousness, language, vision, motor and sensory involvement, as well as some cognitive assessments. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. | 
| Change in Modified Rankin Scale | Single item, global outcomes rating scale for patients post-stroke. Range is from 0-6. Zero being no symptoms and 6 being dead. In-between measures consist of how much help they require during their activities of daily living. | Assessments will be taken at baseline and after treatment (about 2 weeks) to determine change in the score after the treatments or sham stimulation has been given. |