Neurostimulation and Motor Training for Spinal Cord Injury

Overseen By Kyle J O'Laughlin, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: The Cleveland Clinic

Must not be taking: Bupropion, Amphetamines

Disqualifiers: Seizure history, Stroke, Parkinson's, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4-6 hours per session

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with spinal cord injuries improve motor skills, such as hand movements. It combines paired neurostimulation with specialized motor training to determine if it enhances limb use. The trial includes three groups: one receives the actual treatment (PCMS + Contralateral Motor Training), another receives a placebo version (Sham PCMS + Contralateral Motor Training), and the last group rests (PCMS + Rest). Individuals with a neck-level spinal cord injury who retain some muscle movement might be suitable for this trial. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial excludes people who are currently using medications that can lower the seizure threshold, like bupropion or amphetamines. If you are taking these medications, you would need to stop them to participate.

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

Previous studies have shown that techniques like PCMS (paired corticospinal-motoneuronal stimulation) improve movement abilities after a spinal cord injury. For example, research indicates that PCMS helps individuals with spinal cord injuries gain better muscle control and improve hand movements. Importantly, these studies report that the treatment is generally well-tolerated, with no major side effects noted.

When combined with rest, further studies found that PCMS can alter brain and spinal cord communication, potentially aiding movement recovery. These findings suggest that the treatment is safe and could be a promising method to help individuals with spinal cord injuries regain movement. Overall, the evidence supports the safety of these treatments, though ongoing research will provide more detailed insights. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the PCMS + Contralateral Motor Training treatment because it offers a novel approach to spinal cord injury rehabilitation by combining neurostimulation with targeted motor exercises. Unlike traditional treatments that often focus solely on physical therapy or medication, this treatment uses paired corticospinal-motor stimulation (PCMS) to potentially enhance neural plasticity and recovery. The integration of contralateral motor training aims to promote motor function in affected limbs by leveraging the brain's ability to reorganize and strengthen new pathways. This innovative combination could lead to improved outcomes in motor recovery compared to current standard care options.

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

Research has shown that paired corticospinal-motoneuronal stimulation (PCMS), combined with exercises for the opposite side of the body, can improve movement skills after a spinal cord injury (SCI). In this trial, participants may receive PCMS with contralateral motor training, which studies indicate strengthens brain-to-muscle signals, enhancing movement control. Alternatively, some participants will receive PCMS with rest, or a sham version of the treatment combined with contralateral motor training. One study found that using PCMS with practice helped individuals retain improved skills for at least a week. Overall, PCMS has demonstrated promising results in enhancing movement ability and muscle strength in individuals with SCI. ^{1 2 6 7 8}

Who Is on the Research Team?

Ela Plow, PhD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for individuals with cervical Spinal Cord Injury (SCI) who are interested in improving their motor and hand dexterity skills. Specific eligibility criteria details were not provided, so participants should inquire about inclusion and exclusion requirements.

Inclusion Criteria

I can still move the muscles in my hands, though not fully.

It has been at least a year since my injury.

My spinal cord injury is between C4 and C8.

Exclusion Criteria

I am not currently undergoing any upper-limb therapies.

History of alcohol and/or drug abuse

I have a history of neurological conditions like stroke or Parkinson's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessments including CUE-T, COPM, GRASSP, SCIM, and LTPAQ-SCI are conducted to evaluate participants' initial functional abilities and participation restrictions.

1 week

1 visit (in-person)

Treatment

Participants undergo paired corticospinal-motor neuronal stimulation (PCMS) combined with contralateral motor training or rest, with assessments of spinal and cortical excitability, ballistic acceleration, and finger dexterity.

4-6 hours per session

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in motor function and dexterity post-treatment, including assessments of spinal and cortical excitability and finger dexterity.

4-6 hours

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PCMS + Contralateral Motor Training
• PCMS + Rest
• Sham PCMS + Contralateral Motor Training

Trial Overview

The study tests the effects of paired neurostimulation (PCMS) combined with contralateral motor training versus PCMS with rest or sham PCMS plus training on enhancing motor skills in people with SCI.

How Is the Trial Designed?

Group I: PCMS + Contralateral Motor Training Experimental Treatment 1 Intervention

Group II: PCMS + Rest Active Control 1 Intervention

Group III: Sham PCMS + Contralateral Motor Training Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

The Craig H. Neilsen Foundation

Collaborator

Trials

62

Recruited

3,100+

Published Research Related to This Trial

Increasing the number of paired corticospinal-motoneuronal stimulation (PCMS) pulses from 180 to 360 significantly enhanced corticospinal excitability and voluntary motor output in individuals with chronic incomplete spinal cord injury (SCI).

Participants with SCI showed improved performance on the nine-hole-peg-test (9HPT) after receiving 360 paired pulses, indicating that higher doses of PCMS can effectively boost motor function and may promote spinal plasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased paired stimuli enhance corticospinal-motoneuronal plasticity in humans with spinal cord injury. Grover, FM., Chen, B., Perez, MA.[2023]

Intraspinal microstimulation (ISMS) shows promise for restoring bladder function and facilitating standing and walking movements in animal models after spinal cord injury, indicating its potential therapeutic efficacy.

ISMS works by activating existing spinal cord circuitry, which can lead to fatigue-resistant movements and improved coordination, suggesting a mechanism that could be harnessed for clinical applications in treating spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraspinal microstimulation for the recovery of function following spinal cord injury. Bamford, JA., Mushahwar, VK.[2021]

A novel treatment called high-PAS, which combines high-intensity transcranial magnetic stimulation and high-frequency electrical peripheral nerve stimulation, showed positive therapeutic effects in 20 patients with incomplete spinal cord injuries, improving motor scores and functional independence.

The study indicates that high-PAS can benefit a diverse group of patients, including those with varying injury severity and types, suggesting its potential as a non-invasive and cost-effective approach for spinal cord injury rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel paired associative stimulation protocol with a high-frequency peripheral component: A review on results in spinal cord injury rehabilitation. Shulga, A., Lioumis, P., Kirveskari, E., et al.[2021]

In a study involving 25 individuals with chronic spinal cord injuries, combining rehabilitative exercise with paired corticospinal-motor neuronal stimulation (PCMS) led to a significant 20% improvement in functional recovery, as measured by the GRASSP and 10-m walk test.

The benefits of PCMS were long-lasting, with preserved improvements in muscle response and voluntary contractions observed 6 months post-intervention, indicating that this non-invasive stimulation could enhance the effectiveness of exercise in promoting recovery for individuals with varying levels of paralysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury. Jo, HJ., Perez, MA.[2022]

Electrical stimulation (ES) of the injured corticospinal tract (CST) in a rat model significantly increased axonal collateralization compared to control groups, particularly with the higher frequency stimulation (ES333).

However, while ES improved collateral sprouting, it did not lead to differences in axonal regeneration or functional recovery, indicating that further research is needed to optimize stimulation parameters for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical electrical stimulation in female rats with a cervical spinal cord injury to promote axonal outgrowth. Jack, AS., Hurd, C., Forero, J., et al.[2019]

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]

A 15-day treatment combining high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) with motor training showed potential to enhance corticospinal excitability and improve hand function in a patient with chronic complete spinal cord injury.

The case report indicates that increased training repetitions may be crucial for achieving consistent recovery outcomes, suggesting that further studies with larger groups are needed to validate these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency rTMS Combined with Task-Specific Hand Motor Training Modulates Corticospinal Plasticity in Motor Complete Spinal Cord Injury: A case report. Brihmat, N., Bayram, MB., Allexandre, D., et al.[2022]

Cervical intraspinal microstimulation (ISMS) shows promise in improving forelimb function after incomplete spinal cord injuries, suggesting it can activate spinal circuits below the injury site.

Therapeutic ISMS may support long-term recovery by promoting neuron survival and growth, indicating its potential as a treatment for enhancing motor control in patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery. Mondello, SE., Kasten, MR., Horner, PJ., et al.[2021]

Using more paired corticospinal-motoneuronal stimulation (PCMS) significantly enhances spinal level plasticity, with 100 paired stimuli leading to a 46% to 71% increase in corticospinal transmission compared to only a 6% increase with 50 paired stimuli.

This study suggests that the 100-PCMS technique could be a promising therapeutic approach to improve muscle control in patients with weakened motor function, as it produced more reliable changes in muscle response compared to other methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

More conditioning stimuli enhance synaptic plasticity in the human spinal cord. Fitzpatrick, SC., Luu, BL., Butler, JE., et al.[2017]

In a proof-of-principle study involving two patients with chronic spinal cord injuries, long-term paired associative stimulation (20-24 weeks) led to significant recovery of voluntary movements, including ankle movement in one patient and grasping ability in another.

The improvements in motor function persisted for at least one month after the last stimulation session, suggesting that paired associative stimulation can strengthen neural connections in a clinically relevant way, warranting further research into its potential as a rehabilitation strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. Shulga, A., Lioumis, P., Zubareva, A., et al.[2019]

Citations

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

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sciencedirect.com

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A single session of motor imagery paired with spinal ...

Corticospinal excitability increased after a session of MI paired with TSCS while spinal excitability was not affected. •. MI and TSCS are promising ...

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Noting results of prior therapeutic trials, 18, 19 PCMS may enhance movement potential in specific joint actions that support whole limb behavior to improve ...

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Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients.

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This narrative review examines the current state of evidence regarding the therapeutic use of rTMS for motor function recovery after SCI.

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Paired motor cortex and cervical epidural electrical stimulation ...

Repeated pairing of motor cortex and spinal cord stimulation caused lasting increases in evoked potentials from both sites, but only if the time ...