Non-Invasive Neuromodulation for Spinal Cord Injury

Overseen By Caitlin Hurd, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Alberta

Must be taking: Anti-spasmodics

Disqualifiers: Other nervous system injury, pregnant

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

10 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should be on a stable dose of anti-spasmodics. This suggests you may need to continue those medications.

What data supports the effectiveness of the treatment Paired Corticospinal Motoneuronal Stimulation, Transcutaneous Cervical Spinal Cord Stimulation for spinal cord injury?

Research shows that paired corticospinal-motoneuronal stimulation can enhance nerve transmission in people with spinal cord injuries, and transcutaneous spinal cord stimulation has been found to improve muscle strength and voluntary movement. These treatments help the brain and spinal cord work better together, which can aid recovery in people with spinal cord injuries. ^{1 2 3 4 5}

Is non-invasive neuromodulation for spinal cord injury generally safe for humans?

Research on cervical spinal cord stimulation (cSCS) shows it is relatively safe, with a low risk of complications. A study found a 0.5% rate of spinal cord injury and no deaths among 2053 cases, suggesting it is a safe option for many patients. ^{1 2 6 7 8}

How does the treatment Paired Corticospinal Motoneuronal Stimulation and Transcutaneous Cervical Spinal Cord Stimulation differ from other treatments for spinal cord injury?

This treatment is unique because it combines non-invasive electrical stimulation techniques to enhance communication between the brain and spinal cord, potentially improving motor function in people with spinal cord injuries. Unlike other treatments, it specifically targets and synchronizes stimulation to facilitate plasticity (the brain's ability to change and adapt) in the neural circuits responsible for hand and arm movements. ^{1 2 5 9 10}

Research Team

Jessica M D'Amico, PhD

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for individuals with chronic cervical spinal cord injury who are looking to improve arm and hand function. Participants will undergo two different non-invasive therapies combined with rehabilitation over several months, including a washout period.

Inclusion Criteria

AIS A-D

I am on a stable dose of medication for muscle spasms.

I have a spinal cord injury due to trauma.

Exclusion Criteria

Individuals with injury to the nervous system other than to the spinal cord

Pregnant

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1: tSCS

Participants receive transcutaneous spinal cord stimulation combined with functional task practice for two months

8 weeks

Up to 5 sessions per week

Washout

A washout period to prevent carryover effects between treatment phases

4 weeks

Treatment Phase 2: PCMS

Participants receive paired corticospinal motoneuronal stimulation combined with functional task practice for two months

8 weeks

Up to 5 sessions per week

Follow-up

Participants are monitored for retention of intervention effects and safety

12 weeks

Monthly assessments

Treatment Details

Interventions

• Paired Corticospinal Motoneuronal Stimulation
• Transcutaneous Cervical Spinal Cord Stimulation

Trial Overview The study tests transcutaneous spinal cord stimulation and paired corticospinal-motoneuronal stimulation, each combined with functional task practice. It uses a crossover design so participants experience both treatments in separate phases to compare effectiveness.

Participant Groups

Group I: Cervical Transcutaneous Spinal Cord Stimulation with Functional Task Practice Active Control 2 Interventions

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.

Group II: Paired Corticospinal Motoneuronal Stimulation with Functional Task Practice Active Control 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Praxis Spinal Cord Institute

Collaborator

Trials

5

Recruited

80+

Findings from Research

In a study involving humans with chronic incomplete spinal cord injury (SCI), paired corticospinal-motoneuronal stimulation (PCMS) during voluntary muscle activity (PCMSactive) significantly enhanced corticospinal transmission compared to PCMS at rest (PCMSrest).

The results indicate that engaging in voluntary muscle contractions while undergoing PCMS can improve the effectiveness of the treatment, suggesting a potential strategy to enhance spinal plasticity and recovery in individuals with SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potentiating paired corticospinal-motoneuronal plasticity after spinal cord injury. Bunday, KL., Urbin, MA., Perez, MA.[2019]

Percutaneous magnetic stimulation is a non-invasive technique that can effectively stimulate deep nervous structures, including the cervical spinal cord, with minimal discomfort to patients.

This study provides evidence that this method can directly activate descending systems in the spinal cord, potentially involving cortico-motoneuronal pyramidal axons or the propriospinal system, which may enhance muscle response activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous magnetic stimulation of descending tracts in the cervical spinal cord in humans. Tomberg, C.[2019]

Transcutaneous electrical stimulation of the spinal cord (TESS) significantly enhances motor-evoked potentials in arm muscles for up to 75 minutes after stimulation, indicating its potential to promote functional recovery in individuals with spinal cord injury (SCI).

The study found that TESS has a dual effect: it excites spinal networks while inhibiting cortical activity, which may contribute to improved hand and arm function, especially when using a specific 5 kHz carrier frequency during stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. Benavides, FD., Jo, HJ., Lundell, H., et al.[2021]

In a study analyzing 2053 cases of cervical spinal cord stimulation (cSCS) from 2002 to 2011, the rate of spinal cord injury was found to be 0.5%, which is higher than previously reported, indicating a need for careful patient selection and counseling.

Despite the spinal cord injury rate, cSCS remains a relatively safe procedure with low rates of other complications (1.1% neurological, 1.4% medical, and 11.7% general perioperative complications), making it a viable option for pain management in patients, especially in an aging population reliant on opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of perioperative neurological complications after surgery for cervical spinal cord stimulation. Chan, AK., Winkler, EA., Jacques, L.[2017]

Transcutaneous spinal direct current stimulation (tsDCS) can modulate corticospinal excitability in individuals with chronic incomplete spinal cord injury, showing trends of increased excitability on one side and decreased on the other, depending on the stimulation polarity.

In a study with six participants, no significant differences were found between stimulation conditions, but the results suggest that further research is needed to optimize electrode placement and explore the potential for improved movement function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. Powell, ES., Carrico, C., Salyers, E., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Potentiating paired corticospinal-motoneuronal plasticity after spinal cord injury. [2019]

2. Ireland pubmed.ncbi.nlm.nih.gov

Transcutaneous magnetic stimulation of descending tracts in the cervical spinal cord in humans. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Remodeling Brain Activity by Repetitive Cervicothoracic Transspinal Stimulation after Human Spinal Cord Injury. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Neurophysiological Changes After Paired Brain and Spinal Cord Stimulation Coupled With Locomotor Training in Human Spinal Cord Injury. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Rate of perioperative neurological complications after surgery for cervical spinal cord stimulation. [2017]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Low-Intensity and Short-Duration Continuous Cervical Transcutaneous Spinal Cord Stimulation Intervention Does Not Prime the Corticospinal and Spinal Reflex Pathways in Able-Bodied Subjects. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Selective augmentation of corticospinal motor drive with trans-spinal direct current stimulation in the cat. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. [2018]