Spinal Cord Stimulation to Augment Activity Based Therapy

Study Overview
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Brief Summary
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Involuntary muscle activity, often called spasticity, is a common problem following spinal cord injury (SCI) that can make it hard to move. Many things can cause spasticity including: muscle stretch, movement, or it can happen for no reason, and it is often described as an uncontrolled muscle spasm or feeling of stiffness. Drugs are typically used to treat spasticity, but they often have side effects, like muscle weakness, which can add to movement problems. Rehabilitation therapies offer alternatives to drugs for treating involuntary muscle activity, and rehabilitation can also improve daily function and quality of life. These benefits may be greater when several rehabilitation therapies are used together. Walking ability can be improved with a type of therapy called locomotor training. This type of therapy may also have the benefit of decreasing spasticity. When locomotor training (LT) is combined with electrical stimulation, the benefits of training may be increased. In this study, investigators will use a kind of stimulation called transcutaneous spinal cord stimulation (TSS) to stimulate participants' spinal cord nerves during locomotor training.

Detailed Description
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Involuntary muscle activity, often referred to as spasticity, is a common problem following spinal cord injury. Spasticity can be evoked by stimuli or occur spontaneously, and it can manifest as spasms, clonus, or the stiffness associated with hypertonia. While medications are typically used to treat the general symptoms of spasticity, they often have additional side effects, like muscle weakness, that can impede rehabilitation. Physical therapeutics offer an alternative to these drug treatments, but the most effective therapeutic strategy for managing spasticity has not yet been identified. A combination of physical therapeutics may provide the best strategy for managing spasticity while also improving general motor control for functional movements. Walking ability can be improved through locomotor training, which has also been shown to reduce spasticity. When locomotor training is combined with electrical stimulation, the benefits of training may be increased. To investigate the potential benefits of this combinatorial treatment strategy, investigators will use a kind of electrical stimulation called transcutaneous spinal cord stimulation (TSS) to stimulate spinal cord nerves during locomotor training. In order to facilitate the translation of study findings into clinical practice, this study uses a pragmatic design, meaning that the study will involve the use of real world clinical settings and practices. Participants will undergo their standard physical therapist directed locomotor training program while receiving transcutaneous spinal cord stimulation (TSS) as an additional treatment. The effects of locomotor training alone will be compared to the combination of locomotor training with TSS, specifically comparing the effects of these treatments on spasticity and walking function. Investigators expect that the combination of TSS with locomotor training will provide 1) a greater reduction in spasticity and 2) a greater improvement of walking function compared to locomotor training alone. The findings from this study have the potential to rapidly facilitate the translation of a novel combination treatment for the management of spasticity and improvement of walking function into real world clinical practice.

Official Title
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Combined Influence of Transcutaneous Spinal Cord Stimulation and Locomotor Training on Spasticity and Walking Outcomes After Spinal Cord Injury

Conditions
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Walking, Transcutaneous Spinal Stimulation, Spasticity, Human, Spinal Cord Injuries

Intervention / Treatment
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* Device: Transcutaneous spinal stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability and willingness to consent and/or authorize use of protected health information Be between 18-65 years of age Be enrolled in Spinal Cord Injury In-Patient or Day Program at the Shepherd Center Be eligible for locomotor training at the Shepherd Center Be able to take a step, with or without an assistive device Have a spinal cord injury, completed in-patient rehabilitation, and have been discharged to home Have at least mild spasticity affecting leg muscles You may participate if you use prescription medications, including baclofen for control of spasticity Exclusion Criteria: Inability or unwillingness to consent and/or authorization for use of protected health information Progressive or potentially progressive spinal lesions, including degenerative, or progressive vascular disorders of the spine and/or spinal cord Neurologic level at or below spinal level T12 History of cardiovascular irregularities Problems with following instructions Orthopedic problems that would limit your participation in the protocol (e.g. knee or hip flexion contractures of greater than 10 degrees) Women who are pregnant, or who have reason to believe they are or may become pregnant due to unknown risks to the fetus associated with tcSCS Persons who have implanted stimulators/electronic devices of any type will be excluded due to unknown potential of tcSCS effects Active infection of any type, as infection may exacerbate spasticity resulting in inability to identify the influence of the treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Subthreshold<br>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training. | Device: Transcutaneous spinal stimulation<br>* For TSS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.<br>* Other names: TSS;|
| Experimental: Active<br>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training. | Device: Transcutaneous spinal stimulation<br>* For TSS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.<br>* Other names: TSS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Walking Function - 10m Walk Walking Speed (m/s) | You will walk over a mat that contains sensors to measure your walking speed as well as wear motion tracking sensors. You will be allowed to use whatever assistive devices you typically use (e.g., braces, walker, forearm crutches). In addition to walking speed, we will also assess your gait kinematics. | Change in 10m Walk Speed (m/s) during the Intervention Phase (Week 2 test to Week 4 test) | 
| Change in Spasticity - Pendulum Test | This test measures the amount of spasticity in your leg muscles. You will sit at the edge of a mat with your lower legs hanging over the edge of the mat. Motion capture sensors (Xsens) will be placed on both of your legs to record changes in your knee joint angles when your leg is dropped. The examiner will straighten your leg and then allow it to drop and swing over the edge of the mat. The angle of your knee and the movement of your leg will be recorded as it drops. This will be performed three times for each leg separately. | Pendulum angle (degrees) change during the Intervention Phase (Week 2 test to Week 4 test) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Walking Function - 2 Minute Walk | You will walk for 2 minutes overground and we will measure how far you walk. | 2 Minute Walk test (distance) change during the Intervention Phase (Week 2 test to Week 4 test) | 
| Change in Spasticity - Ankle Clonus Drop Test | This test measures the amount of spasticity in your ankle. We will use the motion capture sensors to record your ankle joint angles. For this test you will sit upright. Your leg will be raised to 10cm above the rest position and released allowing the front of your foot to land on the edge of a box. The angle bouncing movement of your foot (clonus) will be recorded as it drops and catches on the box. This will be performed three times for each leg separately. Full details of test methods can be found at: Manella, Roach, and Field-Fote. Temporal Indices of Ankle Clonus and Relationship to Electrophysiologic and Clinical Measures in Persons With Spinal Cord Injury. J Neurol Phys Ther. 2017 Oct;41(4):229-238. | Change in number of clonic ankle oscillations elicited via Ankle Clonus Drop Test during the Intervention Phase (Week 2 test to Week 4 test) | 
| Change in Spasticity - Muscle Co-contraction During Voluntary Activation | Muscle activity will be recorded using electromyography (EMG) during activities where you move your legs, and activities where your legs are moved by the examiner. Electrodes will be placed on four muscles of your legs (front and back of your thigh and lower leg), you will be asked to move your ankles and extend your legs while we record your muscle activity. We will test whether the EMG is activated in only one muscle (isolated) when you try to activate that muscle, or whether muscles that you are not trying to activate are also activated at the same time (co-contraction) | Co-contraction change during the Intervention Phase (Week 2 test to Week 4 test) | 
| Change in Spasticity - Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) Test | A trained therapist will perform the SCATS assessment before and after each training session. SCATS assesses 3 aspects of spasticity: clonus, flexor spasms, extensor spasms in response to perturbation. Scores range from 0-3 as follows: 0 = no reaction; 1 = mild, <3 sec response; 2 = moderate, 3-10 sec response; 3 = severe, >10 sec response | SCATS scores change during the Intervention Phase (Week 2 test to Week 4 test) | 
| Stimulation Tolerability | Using a 0-10 numerical rating scale (NRS) for pain, you will be asked your perception of pain during the final 2 weeks of stimulation. NRS anchors are 0 = no pain, 10 = pain as bad as you can imagine | Numerical rating scale of painfulness of stimulation in stimulation group only during stimulation weeks only (weeks 3 and 4) |