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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-loop Stimulation | Experimental | Continuous stimulation |
|
| Close-loop Stimulation | Experimental | Intended movement-based stimulation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Open-loop Stimulation | Device | Spinal cord stimulation will be applied continuously over the skin throughout the intervention session. |
|
| 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". |
| 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". |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline- World Health Organization Quality of Life Questionnaire | Self-reported questionnaire on quality of life (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- Spinal Cord Injury - Functional Index Short-Form |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fatma Inanici, MD., Ph.D. | Contact | 206 787 2692 | finanici@uw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Chet Moritz, Ph.D. | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington | Recruiting | Seattle | Washington | 98195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29877852 | Background | Inanici F, Samejima S, Gad P, Edgerton VR, Hofstetter CP, Moritz CT. Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. IEEE Trans Neural Syst Rehabil Eng. 2018 Jun;26(6):1272-1278. doi: 10.1109/TNSRE.2018.2834339. | |
| 33400652 | Background |
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| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
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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.
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Functional measurements and all other assessments will be done by an examiner who does not know the order of the intervention arm.
| Close-loop Stimulation | Device | Spinal cord stimulation will start and stop based on the signals that come from the sensors placed on upper limb muscle surfaces. |
|
| Functional Task Practice | Other | Exercise therapy consists of repeated functional hand and arm movements |
|
|
| 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". |
Patient-reported questionnaire (range 0-100 points, higher score mean better outcome) |
| "Baseline"/"At the end of each treatment arm"/"Through study completion" |
| Change from baseline- International Spinal Cord Injury Bowel Function Basic Data Set.v.2.1 | Patient-reported questionnaire (range 0-47 points, lower score mean better outcome) | "Repeated measurements once every eight weeks throughout the study, an average of 10 months". |
| Change from baseline- Patient Reported Impact of Spasticity Measure | Patient-reported questionnaire (range 0-164 points, lower score mean better outcome) | "Repeated measurements once every eight weeks throughout the study, an average of 10 months". |
| Inanici F, Brighton LN, Samejima S, Hofstetter CP, Moritz CT. Transcutaneous Spinal Cord Stimulation Restores Hand and Arm Function After Spinal Cord Injury. IEEE Trans Neural Syst Rehabil Eng. 2021;29:310-319. doi: 10.1109/TNSRE.2021.3049133. Epub 2021 Mar 2. |
| 26371306 | Background | McPherson JG, Miller RR, Perlmutter SI. Targeted, activity-dependent spinal stimulation produces long-lasting motor recovery in chronic cervical spinal cord injury. Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):12193-8. doi: 10.1073/pnas.1505383112. Epub 2015 Sep 14. |
| D014947 | Wounds and Injuries |