Locomotor Function Following Transcutaneous Electrical Spinal Cord Stimulation in Individuals With Hemiplegic Stroke

Study Overview
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Brief Summary
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This study has two interventional components, the first is a cross-over design and the second is a randomized control trial. Both will evaluate the effectiveness of transcutaneous (non-invasive) spinal cord stimulation on gait and balance function for individuals with hemiplegia due to stroke.

Detailed Description
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OBJECTIVES: Exploratory phase: Identify a systematic, methodical approach to identifying the optimal stimulation parameters and gait training protocol for each individual patient with stroke. Aim 1: Evaluate short-term effects of transcutaneous spinal cord stimulation + gait training on gait symmetry, gait performance, and corticospinal circuitry in individuals with chronic stroke. Aim 2: Evaluate and predict long-term effects of transcutaneous spinal cord stimulation + gait training on gait symmetry, gait performance, and corticospinal circuitry in individuals with chronic stroke Aim 3: Identify parameters that distinguish responders from non-responders to transcutaneous spinal cord stimulation in individuals with chronic stroke.

Official Title
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Locomotor Function Following Transcutaneous Electrical Spinal Cord Stimulation in Individuals With Hemiplegic Stroke

Conditions
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Stroke

Intervention / Treatment
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* Device: Noninvasive spinal stimulation with gait training
* Device: Noninvasive spinal stimulation
* Device: Conventional gait training
* Other: Sham
* Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 18 years or older Able and willing to give written consent and comply with study procedures At least 6 months' post-stroke Hemiplegia secondary to a single stroke Functional Ambulation Category of 2 or greater - i.e., subject needs continuous or intermittent support of one person to help with balance and coordination. Not currently receiving regular physical therapy services Physician approval to participate Exclusion Criteria Ataxia Multiple stroke history Botox injection in lower extremity within the last 4 months Modified Ashworth score of 3 or greater in lower extremity Pregnant or nursing Using a powered, implanted cardiac device for monitoring or support of heart function (i.e. pacemaker, defibrillator, or LVAD) or anti-spasticity implantable pumps Active pressure sores Unhealed bone fractures Peripheral neuropathies Painful musculoskeletal dysfunction due to active injuries or infections Severe contractures in the lower extremities Medical illness limiting the ability to walk Active urinary tract infection Clinically significant depression, psychiatric disorders, or ongoing drug abuse Active cancer or cancer in remission less than 5 years Orthopedic dysfunction, injury, or surgery that would impact an individual's ability to use the lower extremity. Traumatic brain injury or other neurological conditions that would impact the study. TMS-Specific Exclusion Criteria: TMS will be utilized for both Aims. The sub-set of participants who meet these criteria will participate in this component of the studies. Medicated with agents known to increase (e.g., amphetamines) or decrease motor system excitability (e.g., lorazepam) Implanted cardiac pacemaker Metal implants in the head or face Suffers unexplained, recurring headaches Had a seizure in the past unrelated to the stroke event, or has epilepsy Skull abnormalities or fractures A concussion within the last 6 months Unstable cardiorespiratory or metabolic diseases (e.g. cardiac arrhythmia, uncontrolled hypertension, uncontrolled diabetes, or chronic emphysema)

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aim 1: Gait Training + Stimulation<br>Up to 60 min of locomotion training with transcutaneous spinal cord stimulation. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression. | Device: Noninvasive spinal stimulation with gait training<br>* Transcutaneous Spinal Cord Neurostimulator will deliver transcutaneous electrical spinal cord stimulation while subjects perform lower limb locomotor activities.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|
| Active Comparator: Aim 1: Stimulation Only<br>Up to 60 minutes of transcutaneous spinal cord stimulation while resting in a comfortable position. | Device: Noninvasive spinal stimulation<br>* Transcutaneous Spinal Cord Neurostimulator will deliver transcutaneous electrical spinal cord stimulation to subjects.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|
| Active Comparator: Aim 1: Gait Training + Sham Stimulation<br>Up to 30 seconds of transcutaneous spinal cord stimulation in order to blind them to the intervention while performing locomotion training. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression. | Device: Conventional gait training<br>* Subjects will receive lower limb locomotion training without transcutaneous spinal cord stimulation. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|
| Sham Comparator: Aim 1: Sham Only<br>Up to 60 minutes of transcutaneous spinal cord stimulation while resting in a comfortable position during which they will receive up to 30 seconds of transcutaneous spinal cord stimulation in order to blind them to the intervention. | Other: Sham<br>* Subject will not receive either transcutaneous electrical spinal cord stimulation or perform lower limb locomotor activities.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|
| Experimental: Aim 2: Gait Training + Stimulation<br>Up to 60 min of locomotion training with transcutaneous spinal cord stimulation. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression. | Device: Noninvasive spinal stimulation with gait training<br>* Transcutaneous Spinal Cord Neurostimulator will deliver transcutaneous electrical spinal cord stimulation while subjects perform lower limb locomotor activities.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|
| Active Comparator: Aim 2: Gait Training + Sham Stimulation<br>Up to 30 seconds of transcutaneous spinal cord stimulation in order to blind them to the intervention while performing locomotion training. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression. | Device: Conventional gait training<br>* Subjects will receive lower limb locomotion training without transcutaneous spinal cord stimulation. However, the amount of time spent in side-lying locomotion training, treadmill training and over ground training will depend on individual tolerance and progression.<br>Other: Exploratory Phase - Optimization of Gait Training and Spinal Stimulation<br>* Subjects may receive various lower limb locomotion training with or without transcutaneous spinal cord stimulation. Training approaches may include but are not limited to single or split belt treadmill and over ground walking. Transcutaneous Spinal Cord Neurostimulator may deliver a variety of transcutaneous electrical spinal cord stimulation to subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gait Symmetry | Participants will ambulate along Gait Rite electronic walkway 3 times per gait speed to evaluate gait pattern at both their self-selected and safe fast gait speed. The GAITRite electronic walkway contains sensor pads encapsulated in a carpet and connected to a computer. The system can be laid over any flat surface and automates measuring temporal and spatial gait parameters. The GAITRite electronic walkway for the study shall be a minimum of 14 feet long. The GAITRite data capture was chosen as measurement of the patient's overall gait quality. | Aim 1: Baseline pre-intervention immediately post intervention for interventions 1, 2, 3 and 4. Aim 2: Baseline pre-intervention, 4 weeks into the intervention, immediately post intervention and 3 months post intervention for intervention 1 and 2. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6 Minute Walk Test | The 6 Minute Walk Test (6MWT) measures the distance a subject can walk indoors on a flat, hard surface in a period of 6 minutes, using assistive devices, as necessary. The test is a reliable and valid evaluation of functional exercise capacity and is used as a sub-maximal test of aerobic capacity and endurance. The test will be used to determine participant's gait efficiency at baseline and at study completion. The walk test is patient self-paced and assesses the level of functional capacity. Patients are allowed to stop and rest during the test, however, the timer does not stop. If the patient is unable to complete the time, the time stopped is noted and reason for stopping prematurely is recorded. This test will be administered while wearing a portable gas analysis system called the Cosmed K4B2 to measure oxygen consumption. This system measures oxygen consumption (VO2) and Carbon-dioxide production (VCO2) in a breath by breath fashion. | Aim 2: Baseline pre-intervention, 4 weeks into the intervention, immediately post intervention and 3 months post intervention for intervention 1 and 2. | 
| Change in 10 Meter Walk Test | This test will examine the patient's gait speed. Patients will be directed to walk 3 times per gait speed to evaluate gait pattern at both their self-selected and safe fast gait speed. Patients will be positioned 1 meter before the start line and instructed to walk the entire distance and past the end line approximately 1 meter. The distance before and after the course are meant to minimize the effect of acceleration and deceleration. Time will be recorded using a stopwatch and recorded to the one hundredth of a second (ex: 2.15 sec). | Aim 1: Baseline pre-intervention immediately post intervention for interventions 1, 2, 3 and 4. Aim 2: Baseline pre-intervention, 4 weeks into the intervention, immediately post intervention and 3 months post intervention for intervention 1 and 2. |