Clinical trial NCT05267951: Closed-loop Spinal Stimulation for Restoration of Upper Extremity Function After Spinal Cord Injury
Official title: Closed-loop Spinal Stimulation for Restoration of Upper Extremity Function After Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Spinal Cord Injuries
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2022-03-07
Enrollment: 9
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change from baseline- Graded Redefined Assessment of Strength, Sensation, and Prehension version 2
timeFrame: "Repeated measurements once every two weeks throughout the study, an average of 10 months".
measure: Change from baseline- Capabilities of Upper Extremity Test
timeFrame: "Repeated measurements once every two weeks throughout the study, an average of 10 months".
measure: Change from baseline- Grip and Pinch Force
timeFrame: "Repeated measurements once every two weeks throughout the study, an average of 10 months".
measure: Change from baseline- Modified Ashworth Scale
timeFrame: "Repeated measurements once every two weeks throughout the study, an average of 10 months".
Secondary outcomes:
measure: Change from baseline- International Standards for Neurologic Classification of Spinal Cord Injury - Motor Score
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- International Standards for Neurologic Classification of Spinal Cord Injury - Sensory Score
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- International Standards of Autonomic Functions after Spinal Cord Injury
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- H-Reflex
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- Somatosensory Evoked Potentials
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- Motor Evoked Potentials
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline Spinal Cord Independence Measure Self Report
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
Other outcomes:
measure: Change from baseline- World Health Organization Quality of Life Questionnaire
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- Spinal Cord Injury - Functional Index Short-Form
timeFrame: "Baseline"/"At the end of each treatment arm"/"Through study completion"
measure: Change from baseline- International Spinal Cord Injury Bowel Function Basic Data Set.v.2.1
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
measure: Change from baseline- Patient Reported Impact of Spasticity Measure
timeFrame: "Repeated measurements once every eight weeks throughout the study, an average of 10 months".
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Chet Moritz, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.