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

• ClinicalTrials.gov Identifier: NCT05267951
• Recruitment Status: Recruiting
• First Posted: March 7, 2022
• Last Update Posted: October 17, 2022
• Sponsor: University of Washington
• Information provided by (Responsible Party): Chet Moritz, University of Washington

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries	Device: Open-loop Stimulation; Device: Close-loop Stimulation; Other: Functional Task Practice	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment

Intervention 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 (Outcomes Assessor)
• Masking Description: Functional measurements and all other assessments will be done by an examiner who does not know the order of the intervention arm.
• Primary Purpose: Treatment
• Official Title: Closed-loop Spinal Stimulation for Restoration of Upper Extremity Function After Spinal Cord Injury
• Actual Study Start Date: October 12, 2022
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Change from baseline- World Health Organization Quality of Life Questionnaire [ Time Frame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months". ]
   Self-reported questionnaire on quality of life (range 0-100 points, higher score mean better outcome)
2. Change from baseline- Spinal Cord Injury - Functional Index Short-Form [ Time Frame: "Baseline"/"At the end of each treatment arm"/"Through study completion" ]
   Patient-reported questionnaire (range 0-100 points, higher score mean better outcome)
3. Change from baseline- International Spinal Cord Injury Bowel Function Basic Data Set.v.2.1 [ Time Frame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months". ]
   Patient-reported questionnaire (range 0-47 points, lower score mean better outcome)
4. Change from baseline- Patient Reported Impact of Spasticity Measure [ Time Frame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months". ]
   Patient-reported questionnaire (range 0-164 points, lower score mean better outcome)

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. has cervical (C8 or higher), incomplete (American Spinal Cord Injury Impairment Scale - C or D) traumatic spinal cord injury, minimum 1-year post-injury
2. has difficulty with hand functions in activities of daily living (e.g., dressing, grooming, feeding)
3. stable medical condition without cardiopulmonary disease or autonomic dysreflexia that would contraindicate participation in upper extremity rehabilitation or testing activities
4. capable of performing simple cued motor tasks
5. has ability to attend intervention/functional task training and assessment sessions 3 times/week
6. has adequate social support to participate in all intervention and baseline/follow-up assessment sessions throughout 40 weeks.
7. has ability to read and speak English

Exclusion Criteria:

1. dependent on ventilation support
2. has implanted stimulator (e.g., pacemaker, vagus nerve stimulator, cochlear implant, etc.) or baclofen pump
3. has metallic devices and implants in the head (e.g., deep brain stimulators, aneurysm clips/coils, and stents, vagus nerve stimulators)
4. has a history or current signs/symptoms of syringomyelia (progressive pain, muscle weakness, and/or sensory loss; deterioration of bowel/bladder function)
5. has autoimmune etiology of spinal cord dysfunction/injury
6. has received botulinum toxin injections in upper extremity muscles in the prior 6 months
7. has tendon transfer or nerve transfer surgery in the upper extremity,
8. taking tizanidine, dantrolene or diazepam
9. has history of seizures or increased risk for seizures
10. has history of chronic headaches or migraines
11. has history of neurologic diseases, such as stroke, multiple sclerosis, traumatic brain injury, etc.
12. has peripheral neuropathy (diabetic polyneuropathy, entrapment neuropathy, etc.)
13. has rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.)
14. 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
15. has cardiovascular or musculoskeletal disease or injury that would prevent full participation in physical therapy intervention
16. unhealed fracture, contracture, pressure sore, or frequent urinary tract infections or other illnesses that might interfere with upper extremity rehabilitation or testing activities
17. has a history of severe allergy (i.e., allergic reaction that could not be treated with antihistaminic medication
18. has alcohol and/or drug abuse (subject's verbal statement)
19. has cancer
20. 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.)
21. lack of ability to fully comprehend, cooperate and/or safely perform study procedures in the investigator's opinion/judgment
22. unable to read and/or comprehend the consent form

Contacts and Locations

Contacts

Contact: Fatma Inanici, MD., Ph.D.; 206 787 2692; finanici@uw.edu

Locations

United States, Washington

University of Washington; Recruiting

Seattle, Washington, United States, 98195

Contact: Fatma Inanici, MD, Ph.D. 206-787-2692 finanici@uw.edu

Principal Investigator: Chet T. Moritz, PhD

Sub-Investigator: Fatma Inanici, MD, PhD

Sponsors and Collaborators

University of Washington

Investigators

• Principal Investigator: Chet Moritz, Ph.D.; University of Washington

More Information

Publications:

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.

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.

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.

• Responsible Party: Chet Moritz, Associate Professor: Division of Physical Therapy, University of Washington
• ClinicalTrials.gov Identifier: NCT05267951
• Other Study ID Numbers: STUDY00013469
• First Posted: March 7, 2022
• Last Update Posted: October 17, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System