Neurostimulation and Motor Training for Spinal Cord Injury

Overseen By Kyle J O'Laughlin, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: The Cleveland Clinic

Must not be taking: Bupropion, Amphetamines

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

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The purpose of this study in people living with cervical Spinal Cord Injury (SCI) is to examine the effects of paired neurostimulation (i.e., PCMS) combined with contralateral motor training on inter-limb transfer of ballistic motor and hand dexterity skills.

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.

What data supports the effectiveness of the treatment Neurostimulation and Motor Training for Spinal Cord Injury?

Research shows that paired corticospinal-motoneuronal stimulation (PCMS) can enhance corticospinal transmission and improve voluntary motor control in people with spinal cord injuries. Studies have demonstrated that PCMS, especially when combined with exercise, can lead to significant improvements in motor function and strength, with effects lasting for months after treatment. ^{1 2 3 4 5}

Is neurostimulation and motor training for spinal cord injury safe for humans?

The studies suggest that paired corticospinal-motoneuronal stimulation (PCMS) has been used safely in humans with spinal cord injury, showing increased motor function without reported adverse effects. ^{1 4 6 7 8}

How does the treatment PCMS + Contralateral Motor Training differ from other treatments for spinal cord injury?

This treatment is unique because it combines paired corticospinal-motoneuronal stimulation (PCMS) with motor training, which enhances the communication between the brain and muscles, potentially improving motor function in people with spinal cord injury. Unlike other treatments, it specifically targets and strengthens the neural pathways involved in movement, leading to sustained improvements in motor function. ^{1 4 5 9 10}

Research Team

Ela Plow, PhD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

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

History of alcohol and/or drug abuse

I am not currently undergoing any upper-limb therapies.

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

Trial Timeline

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)

Treatment Details

Interventions

• PCMS + Contralateral Motor Training (Neurostimulation)
• PCMS + Rest (Neurostimulation)
• Sham PCMS + Contralateral Motor Training (Neurostimulation)

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.

Participant Groups

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+

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. [2019]

3. France 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. [2021]

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

Increased paired stimuli enhance corticospinal-motoneuronal plasticity in humans with spinal cord injury. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Corticospinal-motor neuronal plasticity promotes exercise-mediated recovery in humans with spinal cord injury. [2022]

6. United States 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. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

More conditioning stimuli enhance synaptic plasticity in the human spinal cord. [2017]

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

Cortical electrical stimulation in female rats with a cervical spinal cord injury to promote axonal outgrowth. [2019]

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

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery. [2021]

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

Intraspinal microstimulation for the recovery of function following spinal cord injury. [2021]