Upper Limb Rehabilitation Using Non-invasive Spinal Cord Stimulation (CIME_upperlimb)

Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal

Status: Enrolling

Conditions: Spinal Cord Injury (Quadraplegia); Spinal Cord Injury, Acute; Spinal Cord Injury Cervical

Treatments: Other: Protocol 2: Combination of activity-based therapy and facilitatory transcutaneous spinal cord stimulation; Other: Protocol 1: Combination of activity-based therapy and sham spinal cord stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07361627

CRIR 2024-2080

Details and patient eligibility

About

The goal of this study is to evaluate if combining activity-based therapy (ABT) with transcutaneous spinal cord stimulation (tSCS) can improve recovery of arm and hand movement in people with cervical spinal cord injury (SCI). As secondary aims, the study will also investigate at how this combination approach affects the cortical changes in the somatosensory and motor areas of the brain, as well as in the spinal cord and whether it helps participants use their arms more in daily life.

The main questions relevant to this study are:

1. Is it feasible to use the ABT + tSCS combination for improving arm and hand movement more than ABT alone during the sub-acute stage after SCI?
2. Does ABT + tSCS induce neuroplasticity, that is, changes in the brain and spinal cord activity linked to motor and sensory functions?
3. Do participants who receive ABT + tSCS report greater use of their arms in daily activities compared to those who receive ABT only?

In this study, participants will:

• Receive either ABT + tSCS or ABT + sham stimulation (a low-intensity current that does not facilitate the movements)
• Take part in 20 training sessions over 6-8 weeks (3 times per week, 45 min of active training each). During this, they will perform strengthening, task-based training, and mental imagery exercises with a therapist.
• Complete clinical tests and neurophysiological assessments (transspinal electrical stimulation, electroencephalography and transcranial magnetic stimulation) at three time points-- at the start, after training, and one month later to measure recovery and brain activity changes.

Researchers will compare the assessment outcomes across the three time points.

Full description

This study is led by Dorothy Barthélemy (Ph.D, pht, Principal Investigator (PI)), Marika Demers (Ph.D, erg., co-PI), Diana Zidarov (Ph.D, co-PI) and Sujata Sinha (PhD, postdoctoral fellow, project lead). Collaborator includes Victoria Duda (PhD).

Population: individuals with SCI with injury level above T2, falling into American Spinal Injury Association (ASIA) categories A to D, in the sub-acute phase, and of minimum age of 16 years. These participants are in-patients admitted in the Institut de réadaptation Gingras-Lindsay de Montréal, Canada.

Participants will be randomized (1:1 ratio) into two equal groups, ABT + tSCS and ABT + sham stimulation and stratified based on ASIA level, age and sex.

During the training session, the ABT + tSCS group will receive ABT combined with tSCS. The tSCS will be delivered using surface electrode placed between C4 and T1 as a cathode and self-adhesive surface electrodes placed in the clavicular region on both sides as anodes. tSCS will deliver tonic pulses (30 - 100 Hz) and at an intensity that facilitates voluntary movements (usually 15 mA and up), determined prior to the first training session. Each ABT session will include 5 parts:

1. Mental imaging exercises: participants will imagine the movement while following a sequence proposed by therapists.
2. Cardiovascular warm-up exercises: using equipment that will allow the participant to train their cardiovascular system.
3. Weight bearing and stretching exercises: exercises to prepare their upper body muscles for the strengthening exercises.
4. Muscle strengthening exercises: exercises to increase their strength, with adapted equipment if necessary.
5. Activity-based exercises: exercises composed of repetitive that are present in the participant's daily life.

In the ABT+ sham stimulation group, intensity will be set at sensory threshold that will not facilitate any movement (usually 2-3mA). The ABT will be similar to the other group.

Prior to the training, clinical tests will be conducted to assess assess their muscle strength, sensations, and the quality of movements participants can make with their arms. Specifically, the primary measure will consist of the Upper Extremity Motor Score from the with American Spinal Injury Association Impairment Exam. The secondary clinical measures will include the following assessments: the Grasp and Release Test, Monofilaments test, Sensory function of the upper limb dermatomes from C4 to T1, Grip and pinch strength with a dynamometer, Proprioception subtest of the Fugl Meyer Assessment, Tetraplegic Upper Limb Activity Questionnaire (TUAQ) and Finger-to-Nose Test from the Comprehensive Coordination Scale. More details of the measures are in the Outcome Measures section.

For neurophysiological measures, electrophysiological assessments will include transspinal evoked potential (TEP), motor evoked potentials (MEPs) using transcranial magnetic stimulation (TMS) and somatosensory evoked potentials (SSEPs) using electroencephalogram (EEG).

These assessments will be conducted before the training, immediately after the training and one month later.

As for the experiment, 40 participants will be recruited, as determined by a priori power analysis.

For the neuroplasticity evaluation, TEP, TMS and EEG will be used.

1. To assess the excitability of spinal pathways, the non-invasive procedure of single-pulse transcutaneous spinal stimulation (tSCS) will be used. Participants will be comfortably seated in a chair or in their wheelchair. Self-adhesive surface electrodes will be placed over the cervical spine, with the cathode (Dura stick plus double wire, Dura stick, USA) over C4-T1 and anodes over the external part of the clavicles (TENS electrodes, ROHVEMJ). Single-pulse tSCS will be delivered using a constant-current stimulator (DS8R, Digitimer, UK) to induce Transspinal evoked potentials (TEPs). Responses will be recorded from surface electromyography. More details of the measurement are in the Outcome Measures section.
2. To assess changes along the corticospinal tract (motor cortex projections to the spinal cord), a magnetic field using the TMS will be applied to the primary motor cortex (M1) over the representation area of the contralateral bicep brachii muscle (this is the target muscle). This response will be recorded painlessly using surface electromyography (EMG) electrodes placed over the targeted muscle. The entire evaluation, including setup, will take approximately one hour. The responses evoked by TMS, that is, the motor evoked potentials, (MEPs) will be compared across the 3 time frames in each group. Particularly, latency and peak-to-peak amplitude of MEPs will be measured. More details of the measurement are in the Outcome Measures section.

2. To assess changes in brain mechanisms, particularly those related to sensory function, EEG recordings will be performed using Brain Vision's 32-electrode cap, with the Fz electrode used as the reference. Recordings will be obtained using a Brain Vision 32-channel EEG cap referenced to Fz. The median nerve of the upper limb will be electrically stimulated to elicit cortical responses. The entire evaluation duration will be for 90 minutes including the setup.

EEG activity from C3 and C4 corresponding to the contralateral sensorimotor cortex, will be analyzed, focusing on the N20 and P25 somatosensory evoked potential (SSEP) components, which occur approximately 20 ms and 25 ms post-stimulus, respectively. The N20-P25 complex reflects transmission through ascending somatosensory pathways.

N20 refers to the SSEP peaking approximately 20 ms after the onset of electrical stimulation at the ulnar nerve. P25 follows the N20, peaking around 25 ms after stimulus onset. Together, these form the N20-P25 complex, which reflects the transmission along ascending neuronal pathways. The amplitude and latency of the SSEPs will be compared across the 3 time frames in each group. In addition to C3 and C4, the neighboring electrode regions will also be inspected to identify any additional SSEPs that may emerge. More details of the measurement are in the Outcome Measures section.

Enrollment: 40 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• quadraplegic participants with a subacute spinal cord injury (sSCI), defined as the stage of spinal cord damage occurring between 1 week and 6 months post-injury, that fall within the period of at least one year post-injury
• 16 years old or above
• have a lesion between above T2
• residual upper limb movement
• have injury level according to ASIA A to D
• hospitalized in the hospital linked with the research center at Gingras Lindsay Rehabilitation Institute of Montreal, 6300 Darlington, Montreal
• can provide informed consent (no severe cognitive deficits by MoCA)
• be able to follow instructions in French or English

Exclusion criteria

• have a pacemaker
• have active cancer on stimulation site or metastatic cancer
• have unstable health conditions
• have unhealed wound, scar or pain which makes positioning of the electrodes impossible
• participants with specific contraindications to TMS (epilepsy, non-union cranial fracture and increased intracranial pressure) will be able to participate in the study, but will not receive TMS

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 2 patient groups

Activity-based therapy with sham spinal stimulation (n=20)

Sham Comparator group

Description:

Participants with cervical spinal cord injury (ASIA levels A-D) randomized to this arm will receive sham transcutaneous spinal cord stimulation combined with activity-based therapy. Training will consist of 20 sessions delivered over 6-8 weeks during the subacute stage. For the transcutaneous spinal cord stimulation (tSCS), a single or two self-adhesive cathode electrodes will be placed at the C4 to T1 vertebral levels. A pair of reference electrodes will be placed bilaterally on the external part of the clavicular regions. The stimulation will be set at minimal intensity, sufficient only for the participants to perceive it.

Treatment:

Other: Protocol 1: Combination of activity-based therapy and sham spinal cord stimulation

Activity-based therapy with facilitatory spinal stimulation (n=20)

Experimental group

Description:

Participants with cervical spinal cord injury (ASIA levels A-D) randomized to this arm will receive real-intensity transcutaneous spinal cord stimulation combined with activity-based therapy. Training will consist of 20 sessions delivered over 6-8 weeks during the subacute stage. For the transcutaneous spinal cord stimulation (tSCS), a single or two self-adhesive cathode electrodes will be placed at the C4 to T1 vertebral levels. A pair of reference electrodes will be placed bilaterally on the external part of the clavicular regions. The stimulation will be set at minimal intensity, sufficient only for the participants to perceive it. Individualized tSCS parameters (30-80Hz, 0-90mA, biphasic 400us pulse square) will be used to facilitate upper limb movement.

Treatment:

Other: Protocol 2: Combination of activity-based therapy and facilitatory transcutaneous spinal cord stimulation