Neuromodulation for Spinal Cord Injury

Overseen By Matija Milosevic, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Miami

Must not be taking: Investigational drugs

Disqualifiers: Traumatic brain injury, Stroke, Epilepsy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to explore the effect of magnetic stimulation to activate the brain, electrical spinal cord stimulation to activate spinal cord, and electrical muscle stimulation used to activate upper limb (arms), lower limb (legs) and trunk (stomach) muscles in people with spinal cord injury (SCI) and able-bodied subjects (without SCI).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on investigational drugs or any intervention that affects neuromotor function, you may not be eligible to participate.

What data supports the effectiveness of the treatment Repetitive Synchronized Associative Stimulation Neuromodulation for spinal cord injury?

Research shows that paired associative stimulation (PAS), a component of the treatment, can improve hand function and reduce pain in patients with spinal cord injuries. It works by strengthening nerve connections in the spinal cord, which may help with motor rehabilitation and pain relief. ^{1 2 3 4 5}

Is neuromodulation for spinal cord injury safe for humans?

Paired associative stimulation (PAS), a type of neuromodulation, is generally considered safe with rare cases of adverse effects reported in patients with spinal cord injuries. ^{1 3 6 7 8}

How is Repetitive Synchronized Associative Stimulation Neuromodulation different from other treatments for spinal cord injury?

This treatment is unique because it uses a non-invasive method called paired associative stimulation (PAS), which combines brain and nerve stimulation to strengthen neural connections and improve motor function in spinal cord injury patients. Unlike other treatments, PAS can lead to long-lasting improvements in voluntary movement and pain relief without the need for drugs. ^{1 3 6 7 9}

Research Team

Matija Milosevic, PhD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for individuals with spinal cord injuries and also includes able-bodied participants. The study aims to understand the effects of different types of stimulation on brain, spinal cord, and muscle activity.

Inclusion Criteria

I am physically able.

I can still move or feel my lower-limb muscles on at least one side.

My trunk muscles show activity when tested with special equipment.

Exclusion Criteria

I have nerve damage, including from diabetes or trapped nerves.

I am not on any experimental drugs affecting movement.

I have a history of epilepsy or seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive magnetic stimulation to activate the brain, electrical spinal cord stimulation, and electrical muscle stimulation for up to 2 months

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Repetitive Synchronized Associative Stimulation Neuromodulation

Trial Overview The trial tests magnetic brain stimulation (iTBS), electrical spinal cord stimulation (TSCS), and muscle activation via functional electrical stimulation (FES). A sham iTBS serves as a control to compare against real treatments.

Participant Groups

Group I: Upper-limb (arms) target group Experimental Treatment 4 Interventions

Quadriplegic individuals with SCI who are primary non-ambulatory (walking) will be in this group for up to 2 months.

Group II: Trunk (torso) target group Experimental Treatment 4 Interventions

Quadriplegic or paraplegic individuals with SCI who are primary wheelchair users will be in this group for up to 2 months.

Group III: Lower-limb (legs) target group Experimental Treatment 4 Interventions

Quadriplegic or paraplegic individuals with SCI primary who can walk will be in this group for up to 2 months.

Group IV: Able-bodied target group Active Control 4 Interventions

Individuals with no spinal cord injury will be in this group for up to 2 months.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

Long-term paired associative stimulation (PAS) was found to be a safe and effective treatment for improving hand motor function in five patients with non-traumatic tetraplegia, with significant improvements observed in manual muscle testing and other functional assessments over a 6-week period and follow-ups.

All patients showed consistent improvements in muscle strength and hand function, with a mean increase of 1.44 points in manual muscle testing immediately after PAS and sustained improvements at 1 and 6 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series. Tolmacheva, A., Savolainen, S., Kirveskari, E., et al.[2022]

A 47-year-old man with incomplete paraplegia showed significant improvement in mobility after receiving paired associative stimulation (PAS) for 6 months, enabling him to stand and walk independently with a rollator, which he could not do before treatment.

The study indicates that PAS, combining transcranial magnetic stimulation and peripheral nerve stimulation, can effectively promote walking rehabilitation in paraplegic patients without any adverse effects, suggesting its potential as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report. Shulga, A., Savolainen, S., Kirveskari, E., et al.[2021]

Paired associative stimulation (PAS) showed promising results in reducing severe drug-resistant neuropathic pain in a 50-year-old man with spinal cord injury, with pain scores decreasing by 44% after two weeks of therapy.

The therapy not only alleviated pain but also improved hand motor function and quality of sleep, suggesting that PAS may modulate pain pathways at the spinal cord level and could be a valuable adjunct treatment for neuropathic pain following spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report. Vaalto, S., Nyman, AL., Shulga, A.[2021]

A new method for spinal paired associative stimulation (PAS) in lower limbs effectively enhances corticospinal transmission by individually estimating interstimulus intervals (ISIs) based on F-response and motor-evoked potential (MEP) latencies, achieving a significant 186% increase in MEP amplitude in healthy subjects.

This approach improves the precision of spinal PAS by ensuring accurate placement of peripheral nerve stimulation electrodes and using navigation in transcranial magnetic stimulation, making it a promising technique for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. Shulga, A., Lioumis, P., Kirveskari, E., et al.[2015]

The study compared different frequencies of paired associative stimulation (PAS) applied to the spinal cord, including 0.1 Hz, 1 Hz, and 5 Hz bursts, but none were effective in consistently inducing neuroplasticity.

High variability in responses among participants indicates that spinal PAS may not be universally effective, suggesting that its therapeutic potential could depend on individual differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract. McGie, SC., Masani, K., Popovic, MR.[2021]

Paired associative stimulation (PAS) is a safe and noninvasive neuromodulation technique that has shown statistically significant improvements in motor functions for patients with spinal cord injuries, with very few reported adverse effects.

The review highlights the need for further standardization of PAS methods, suggesting that with proper refinement, it could become an effective treatment option for the rehabilitation of spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Cord Injury: Lessons about Neuroplasticity from Paired Associative Stimulation. Ling, YT., Alam, M., Zheng, YP.[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 10 healthy subjects, paired associative stimulation (PAS) with high-frequency peripheral nerve stimulation (PNS) showed significant motor-evoked potential (MEP) potentiation when using a baseline PNS intensity or a 25% lower intensity, indicating these levels are optimal for enhancing muscle activity.

Using a higher intensity (25% above baseline) or a much lower intensity (50% below baseline) did not produce significant MEP changes, suggesting that precise control of PNS intensity is crucial for effective PAS outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects. Pohjonen, M., Nyman, AL., Kirveskari, E., et al.[2022]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series. [2022]

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

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. [2015]

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

Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract. [2021]

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

Spinal Cord Injury: Lessons about Neuroplasticity from Paired Associative Stimulation. [2021]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Optimal peripheral nerve stimulation intensity for paired associative stimulation with high-frequency peripheral component in healthy subjects. [2022]

9. 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]