Closed-loop Spinal Stimulation for Restoration of Upper Extremity Function After Spinal Cord Injury

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of non-invasive (transcutaneous) closed-loop electrical spinal cord stimulation for recovery of upper limb function (Aim 1) and spasticity (Aim 2) following spinal cord injury.

Detailed Description
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After being informed about the purpose, study timeline, and procedures, all participants giving written informed consent will undergo repeated baseline measurements throughout four weeks, followed by intensive exercise therapy for six weeks. Next, participants will receive (1) closed-loop stimulation and (2) open-loop stimulation treatment for Aim 1 Section of the study. Stimulation will be delivered non-invasively using skin electrodes on the back of the neck. Each treatment arm will last six weeks. The investigators will determine the order of the treatment arms randomly. For closed-loop stimulation, The investigators will place a sensor on the arm muscles over the skin. This sensor will detect the movement and start the stimulation accordingly. For Aim 2 Section, intervention arms will consist of (1) transcutaneous stimulation, followed by (2) spasticity-reducing stimulation treatment arms. There will be a 6-week waiting period between two stimulation arms where participants will not receive any stimulation or exercise therapy. Treatments will last 90 minutes per session, three sessions per week. Overall participation in the study will last ten months: Four weeks baseline + three treatment periods (each will last six weeks) + six weeks waiting period between stimulation treatments + 12 weeks follow-up.

Official Title
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Closed-loop Spinal Stimulation for Restoration of Upper Extremity Function After Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Open-loop Stimulation
* Device: Close-loop Stimulation
* Other: Functional Task Practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: has cervical (C8 or higher), incomplete (American Spinal Cord Injury Impairment Scale - C or D) traumatic spinal cord injury, minimum 1-year post-injury has difficulty with hand functions in activities of daily living (e.g., dressing, grooming, feeding) stable medical condition without cardiopulmonary disease or autonomic dysreflexia that would contraindicate participation in upper extremity rehabilitation or testing activities capable of performing simple cued motor tasks has ability to attend intervention/functional task training and assessment sessions 3 times/week has adequate social support to participate in all intervention and baseline/follow-up assessment sessions throughout 40 weeks. has ability to read and speak English Exclusion Criteria: dependent on ventilation support has implanted stimulator (e.g., pacemaker, vagus nerve stimulator, cochlear implant, etc.) or baclofen pump has metallic devices and implants in the head (e.g., deep brain stimulators, aneurysm clips/coils, and stents, vagus nerve stimulators) has a history or current signs/symptoms of syringomyelia (progressive pain, muscle weakness, and/or sensory loss; deterioration of bowel/bladder function) has autoimmune etiology of spinal cord dysfunction/injury has received botulinum toxin injections in upper extremity muscles in the prior 6 months has tendon transfer or nerve transfer surgery in the upper extremity, taking tizanidine, dantrolene or diazepam has history of seizures or increased risk for seizures has history of chronic headaches or migraines has history of neurologic diseases, such as stroke, multiple sclerosis, traumatic brain injury, etc. has peripheral neuropathy (diabetic polyneuropathy, entrapment neuropathy, etc.) has rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) has significant medical disease; including uncontrolled systemic hypertension with values above 170/100 mmHg; cardiac or pulmonary disease; uncorrected coagulation abnormalities or need for therapeutic anticoagulation has cardiovascular or musculoskeletal disease or injury that would prevent full participation in physical therapy intervention unhealed fracture, contracture, pressure sore, or frequent urinary tract infections or other illnesses that might interfere with upper extremity rehabilitation or testing activities has a history of severe allergy (i.e., allergic reaction that could not be treated with antihistaminic medication has alcohol and/or drug abuse (subject's verbal statement) has cancer pregnant (Childbearing potential will be asked at screening, baseline, and every subsequent visit in which the subject would receive transcutaneous spinal cord stimulation and/or Transcranial Magnetic Stimulation whether the participant could be pregnant. Pregnancy will be ruled out by an over-the-counter urine pregnancy test for all females of childbearing potential (1) at the time of enrollment, (2) prior to all sessions that include Transcranial Magnetic Stimulation, and also prior to the intervention phases of (3) closed-loop or (4) open-loop stimulation. Additional pregnancy tests may be performed if there is a concern of pregnancy.) lack of ability to fully comprehend, cooperate and/or safely perform study procedures in the investigator's opinion/judgment unable to read and/or comprehend the consent form

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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: Crossover Assignment
Interventional Model Description: Participants who participate in Aim 1 Section of the study will receive open-loop and closed-loop stimulation intervention arms in a randomized order. The order of the two interventions in the Aim 2 Section of the study will be the same for all participants enrolled in the Aim 2 Section of the study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-loop Stimulation<br>Continuous stimulation | Device: Open-loop Stimulation<br>* Spinal cord stimulation will be applied continuously over the skin throughout the intervention session.<br>Other: Functional Task Practice<br>* Exercise therapy consists of repeated functional hand and arm movements<br>* Other names: Intensive exercise therapy;|
| Experimental: Close-loop Stimulation<br>Intended movement-based stimulation. | Device: Close-loop Stimulation<br>* Spinal cord stimulation will start and stop based on the signals that come from the sensors placed on upper limb muscle surfaces.<br>Other: Functional Task Practice<br>* Exercise therapy consists of repeated functional hand and arm movements<br>* Other names: Intensive exercise therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline- Graded Redefined Assessment of Strength, Sensation, and Prehension version 2 | Measurement of upper limb strength, sensation, qualitative prehension, and quantitative prehension (range 0-188, higher score mean better outcome) | Repeated measurements once every two weeks throughout the study, an average of 10 months. | 
| Change from baseline- Capabilities of Upper Extremity Test | Measures unilateral and bilateral hand and arm function (range 0-128, higher score mean better outcome) | Repeated measurements once every two weeks throughout the study, an average of 10 months. | 
| Change from baseline- Grip and Pinch Force | Grip and pinch force measurement using a dynamometer (higher score mean better outcome) | Repeated measurements once every two weeks throughout the study, an average of 10 months. | 
| Change from baseline- Modified Ashworth Scale | Clinician administered assessment of spasticity (range 0-4, lower score mean better outcome) | Repeated measurements once every two weeks throughout the study, an average of 10 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline- International Standards for Neurologic Classification of Spinal Cord Injury - Motor Score | Standard manual muscle strength examination (Range 0-100 points, higher score mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline- International Standards for Neurologic Classification of Spinal Cord Injury - Sensory Score | Standard examination of dermatomal sensation (range 0-224 points, higher score mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline- International Standards of Autonomic Functions after Spinal Cord Injury | Clinician assessment to document remaining autonomic functions after spinal cord injury | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline- H-Reflex | Electrophysiologic measurement of H-reflex (lower Hmax/Mmax ratio mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline- Somatosensory Evoked Potentials | Electrophysiologic evaluation of sensory pathways between the brain and the limb (shorter latency mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline- Motor Evoked Potentials | Electrophysiologic evaluation of motor pathways between the brain and the muscles (higher amplitude mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. | 
| Change from baseline Spinal Cord Independence Measure Self Report | Quantification of the level of independence in daily activities (range 0-100 points, higher score mean better outcome) | Repeated measurements once every eight weeks throughout the study, an average of 10 months. |