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

Spinal Cord Injuries Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05267951
• Other study ID #: STUDY00013469
• Status: Recruiting
• Phase: N/A
• Start date: October 12, 2022
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: University of Washington
• Contact: Fatma Inanici, MD., Ph.D.
• Phone: 206 787 2692
• Email: finanici[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Device:
• Open-loop Stimulation
Spinal cord stimulation will be applied continuously over the skin throughout the intervention session.
• 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

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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".
Other	Change from baseline- Spinal Cord Injury - Functional Index Short-Form	Patient-reported questionnaire (range 0-100 points, higher score mean better outcome)	"Baseline"/"At the end of each treatment arm"/"Through study completion"
Other	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".
Other	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".
Primary	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".
Primary	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".
Primary	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".
Primary	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	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".
Secondary	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".
Secondary	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".
Secondary	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".
Secondary	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".
Secondary	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".
Secondary	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".