Non-Invasive Neuromodulation for Upper Extremity Function in Spinal Cord Injury: A Crossover Trial

NCT06903416 | Recruiting Phase 2

• 1 other identifier: Pro00149698
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study explores two promising therapies for restoring arm and hand function in people with chronic cervical spinal cord injury (SCI), a condition that affects independence and quality of life. It will compare transcutaneous spinal cord stimulation and paired corticospinal-motoneuronal stimulation, both combined with rehabilitation. Using a crossover design, participants will receive each therapy for two months, with a one-month washout period in between. Safety, effectiveness, and patient-reported outcomes like daily living ability and quality of life will be assessed, alongside changes in neural excitability. The results of this study may enable us to tailor treatments to individual needs, promoting personalized care and improved outcomes.

Conditions

Spinal Cord Injury Cervical

Outcome Measures

Primary Outcomes (2)

• International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI)

  The ISNCSCI and its associated subscores related to upper extremity motor and sensory scores will be completed by a blinded assessor.

  Baseline, 2 months (end of block 1), 3 months (start of block 2), 5months (end of block 2) and 8 months (follow-up)

• Graded Redefined Assessment of Strength Sensation and Performance (GRASSP)

  The GRASSP will be assessed by a blinded assessor to evaluate changes in strength, sensation and performance of the upper extremities.

  Baseline, 2 months (end of block 1), 3 months (start of block 2), 5months (end of block 2) and 8 months (follow-up)

Secondary Outcomes (2)

• Spinal excitability - Cervical Multisegmental Motor Responses (cMMR)

  Baseline, 1 month (mid-block 1), 2 months (end of block 1), 3 months (start of block 2), 4 months (mid block 2), 5months (end of block 2) and 8 months (follow-up)

• Corticospinal Excitability-Transcranial magnetic stimulation (TMS)

  Baseline, 1 month (mid-block 1), 2 months (end of block 1), 3 months (start of block 2), 4 months (mid block 2), 5months (end of block 2) and 8 months (follow-up)

Other Outcomes (3)

• SCIM III

  Baseline, 2 months (end of block 1), 3 months (start of block 2), 5months (end of block 2) and 8 months (follow-up)

• WHOQoL-BREF

  Baseline, 2 months (end of block 1), 3 months (start of block 2), 5months (end of block 2) and 8 months (follow-up)

• Patient Global Impression of Change (PGIC) Score

  Month 2 (end of block 1), and Month 5 (end of block 2)

Study Arms (2)

Cervical Transcutaneous Spinal Cord Stimulation with Functional Task Practice

ACTIVE COMPARATOR

Cervical transcutaneous spinal cord stimulation will be delivered following previously reported guidelines. Circular (1.25") electrodes will be placed over the cervical spinal cord between the C3 and C4 vertebral level, with rectangular return electrodes placed either over the clavicles or iliac crests. Biphasic stimulation will be delivered continuously at 30Hz, with a 1ms pulse width, and overlapping 10kHz carrier frequency (Gelenitis et al 2024; Moritz et al 2024). Stimulation will be delivered at a current intensity below motor threshold, that is below the intensity required to elicit a muscle twitch. Cervical tSCS will be delivered for at least 60 minutes during each training session, and FTP will occur during the active stimulation.

Other: Transcutaneous Cervical Spinal Cord Stimulation; Other: Functional Task Practice

Paired Corticospinal Motoneuronal Stimulation with Functional Task Practice

ACTIVE COMPARATOR

Paired transcranial magnetic stimulation and nerve stimulation will be implemented following a previously-published protocol for individuals with SCI (Jo et al 2023). Two figure-eight coils will be used to deliver bilateral magnetic stimulation of the motor cortex and will be combined with synchronous electrical stimulation of the brachial plexus and ulnar nerves, bilaterally. The timing of stimuli will be determined to ensure that electrical volleys arrive at the corticospinal motoneuronal synapse at an appropriate interval to induce long term potentiation. During each session, 360 paired stimuli will be delivered at a frequency of 0.2 Hz. The stimulation paradigm should take approximately 30 minutes. Following this, participants will then complete 60 minutes of FTP.

Other: Paired Corticospinal Motoneuronal Stimulation; Other: Functional Task Practice

Interventions

Transcutaneous Cervical Spinal Cord Stimulation OTHER

Cervical transcutaneous spinal cord stimulation will be delivered following previously reported guidelines. Circular (1.25") electrodes will be placed over the cervical spinal cord between the C3 and C4 vertebral level, with rectangular return electrodes placed either over the clavicles or iliac crests. Biphasic stimulation will be delivered continuously at 30Hz, with a 1ms pulse width, and overlapping 10kHz carrier frequency (Gelenitis et al 2024; Moritz et al 2024). Stimulation will be delivered at a current intensity below motor threshold, that is below the intensity required to elicit a muscle twitch. Cervical tSCS will be delivered for at least 60 minutes during each training session, and FTP will occur during the active stimulation.

Cervical Transcutaneous Spinal Cord Stimulation with Functional Task Practice

Paired Corticospinal Motoneuronal Stimulation OTHER

Paired transcranial magnetic stimulation and nerve stimulation will be implemented following a previously-published protocol for individuals with SCI (Jo et al 2023). Two figure-eight coils will be used to deliver bilateral magnetic stimulation of the motor cortex and will be combined with synchronous electrical stimulation of the brachial plexus and ulnar nerves, bilaterally. The timing of stimuli will be determined to ensure that electrical volleys arrive at the corticospinal motoneuronal synapse at an appropriate interval to induce long term potentiation. During each session, 360 paired stimuli will be delivered at a frequency of 0.2 Hz. The stimulation paradigm should take approximately 30 minutes. Following this, participants will then complete 60 minutes of FTP.

Paired Corticospinal Motoneuronal Stimulation with Functional Task Practice

Functional Task Practice OTHER

A typical rehabilitation program will be defined and delivered in consultation with physical and occupational therapists. The program will consist of functional tasks including repetitive activities of gross upper extremity movement, isolated finger movements, simple and complex pinch, and grasping activities. For each category, 4-10 activities with various difficulty levels will be identified. Each participant will perform at least 1-2 exercises within each category during each treatment session. Activities in each category will be chosen according to the participants' ability and adjusted based on the evolution of the ability to perform the functional task over time (graded training).

Cervical Transcutaneous Spinal Cord Stimulation with Functional Task Practice; Paired Corticospinal Motoneuronal Stimulation with Functional Task Practice

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cervical (C2-C8) level SCI
• \> 9 months post-injury
• Traumatic SCI
• AIS A-D
• Stable dose of anti-spasmodics

You may not qualify if:

• individuals with injury to the nervous system other than to the spinal cord
• pregnant

Sponsors & Collaborators

• University of Alberta: lead
• Praxis Spinal Cord Institute: collaborator

Study Sites (1)

Glenrose Rehabilitation Hospital

Edmonton, Alberta, T5G0B7, Canada

RECRUITING

Study Officials

• Jessica M D'Amico, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica M D'Amico, PhD

CONTACT

7802039478; damico1@ualberta.ca

Caitlin Hurd, PhD

CONTACT

caitlin.hurd@ahs.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 30, 2025
• Study Start: May 7, 2025
• Primary Completion (Estimated): March 30, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)