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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve arm and hand function in individuals with long-term spinal cord injuries affecting the neck area. It tests two treatments: one involves electrical stimulation on the spine (Transcutaneous Cervical Spinal Cord Stimulation), and the other combines brain and nerve stimulation (Paired Corticospinal Motoneuronal Stimulation), both paired with exercises. Participants will undergo each therapy for two months to assess improvements in everyday tasks and overall quality of life. Individuals who have experienced a traumatic spinal injury in the neck (C2-C8) for over nine months and are managing spasms with stable medication may be suitable candidates. As a Phase 2, Phase 3 trial, this study evaluates treatment effectiveness in a smaller group and represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transcutaneous cervical spinal cord stimulation (tSCS) is safe. Studies have found that both children and adults with spinal cord injuries tolerate this method well. One study discovered that it improved arm strength and control without causing harm. Another study confirmed that tSCS met all safety goals, indicating it does not pose serious risks.

For paired corticospinal motoneuronal stimulation, research also supports its safety. Studies show that participants tolerate this therapy well, with no major problems reported during trials. This method strengthens nerve connections, improving movement without causing dangerous side effects.

Both therapies are in advanced testing stages, having already passed earlier safety checks. This suggests they are likely safe for participants in the current trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for spinal cord injury because they offer non-invasive alternatives that may enhance recovery by directly stimulating neural pathways. Unlike traditional rehabilitation methods, which often focus on physical therapy alone, cervical transcutaneous spinal cord stimulation uses electrical stimulation to activate neural circuits below the level of injury without causing muscle twitches, potentially improving motor function. Meanwhile, paired corticospinal motoneuronal stimulation combines magnetic and electrical stimulation to synchronize with the body’s natural nerve signals, aiming to strengthen synaptic connections for long-term recovery. These innovative approaches could lead to more effective and efficient rehabilitation outcomes for individuals with spinal cord injuries.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

This trial will compare two treatments for spinal cord injury: transcutaneous cervical spinal cord stimulation (tSCS) and paired corticospinal-motoneuronal stimulation (PCMS). Research has shown that tSCS can enhance hand and arm function in individuals with spinal cord injuries, increasing grip strength and aiding movement tasks. When combined with rehabilitation, it has improved mobility for many. Meanwhile, studies on PCMS have demonstrated significant improvements in hand strength and control, with patients experiencing better walking speed and grasping ability, and these benefits lasting for several months. Both therapies offer promising results for enhancing recovery in individuals with spinal cord injuries. ^{1 2 6 7 8}

Who Is on the Research Team?

Jessica M D'Amico, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 have a spinal cord injury due to trauma.

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

Exclusion Criteria

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

Pregnant

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36752493/

Increased paired stimuli enhance corticospinal-motoneuronal ... Our findings demonstrate that increasing the number of PCMS paired pulses potentiates corticospinal excitability and voluntary motor output after SCI.

2. tandfonline.com tandfonline.com/doi/full/10.1080/10790268.2021.1970908

Full article: Paired corticospinal-motoneuronal stimulation ... There were also significant improvements in functional outcomes, including walking speed and grasping function, which persisted after 6–9 months ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878747925002569

Paired associative stimulation improves outcomes when ... Patients with incomplete cervical SCI were randomized 1:1 within 1–4 months post-injury to receive 12 weeks of PAS or sham stimulation alongside ...

4. journals.physiology.org journals.physiology.org/doi/pdf/10.1152/jn.00499.2022

Increased paired stimuli enhance corticospinal- ... Paired corticospinal-motoneuronal stimulation (PCMS) has been used to enhance corticospinal excitability and functional outcomes.

5. physoc.onlinelibrary.wiley.com physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP287204

Paired corticospinal‐motoneuronal stimulation enhances ... A single session of PCMS improves long-term retention following ballistic motor learning.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34779722/

Paired corticospinal-motoneuronal stimulation and exercise ... Conclusions: Voluntary movement is enhanced in people with SCI through the strengthening of corticospinal-motoneuronal synapses using paired stimulation. This ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X18301530

Potentiating paired corticospinal-motoneuronal plasticity ... Corticospinal transmission was significantly improved after active PCMS in those SCI individuals that did not respond well at rest.

8. nature.com nature.com/articles/s41598-024-82271-4

Spinally targeted paired associative stimulation with high ... This study revealed the effects of spinally and cortically targeted high-PAS in healthy subjects. As anticipated, both interventions ...