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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Repetitive Synchronized Associative Stimulation Neuromodulation. It examines how different types of stimulation—magnetic for the brain, electrical for the spinal cord, and electrical for muscles—can assist people with spinal cord injuries. The trial includes various groups: able-bodied individuals, people with SCI using wheelchairs, those who can walk, and those with limited arm use. Ideal candidates for this trial have had a spinal cord injury for over 6 months and retain some muscle movement, even if minimal. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatments for spinal cord injuries.

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 prior data suggests that this neuromodulation technique is safe for spinal cord injury and able-bodied subjects?

Research has shown that Repetitive Synchronized Associative Stimulation Neuromodulation is generally safe. Studies have found it to be well-tolerated, with rare reports of serious side effects. This treatment combines magnetic and electrical stimulation to activate the brain and muscles.

Patients in earlier studies found it safe and practical, even when used soon after a spinal cord injury. Overall, the evidence suggests that this treatment typically does not cause major problems for users. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Repetitive Synchronized Associative Stimulation Neuromodulation for spinal cord injury because it offers a novel approach to rehabilitation. Unlike traditional treatments that often rely on physical therapy and medication to manage symptoms, this method harnesses neuromodulation, which involves directly stimulating the nervous system to encourage recovery. This technique is particularly promising because it aims to retrain the brain and spinal cord to communicate more effectively, potentially improving motor function in a way that current treatments, like physical therapy and medications, may not fully achieve. By targeting the nervous system directly, it could offer quicker and more significant improvements for individuals with spinal cord injuries.

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

Research shows that a treatment called repetitive synchronized associative stimulation, which includes paired associative stimulation (PAS), can improve movement and reduce pain in people with spinal cord injuries. This trial will evaluate the effects of this treatment across different groups, including those targeting the upper limbs, trunk, and lower limbs, as well as an able-bodied comparator group. Studies have found that PAS can enhance hand function and improve movement, especially when used soon after an injury. This treatment uses magnetic and electrical signals to stimulate the brain, spinal cord, and muscles, helping them coordinate better. Early findings suggest that this method is promising for rehabilitation, offering hope for better movement and less pain for those affected. Overall, the treatment has shown encouraging results in improving motor skills and quality of life for people with spinal cord injuries. ^{1 3 4 5 6}

Who Is on the Research Team?

Matija Milosevic, PhD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

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

Paired associative stimulation improves outcomes when ... Paired associative stimulation improves outcomes when applied at the subacute stage after incomplete cervical spinal cord injury. Author ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06494059/a-novel-repetitive-synchronized-associative-stimulation-neuromodulation-approach-for-spinal-cord-injury-patients

A Novel Repetitive Synchronized Associative Stimulation ... The purpose of this research is to explore the effect of magnetic stimulation to activate the brain, electrical spinal cord stimulation to ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38768088/

Paired associative stimulation to enhance motor outcome ... Available evidence showed an increase in motor outcomes after PAS stimulation. Indeed, both clinical and neurophysiological outcomes suggest the effectiveness.

4. withpower.com withpower.com/trial/phase-spinal-cord-injuries-9-2024-f7b6a

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 ...

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

Spinally targeted paired associative stimulation with high- ... High-PAS is a novel PAS variant that has shown promising results in motor rehabilitation of individuals with SCI and these new findings contribute to the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5610384/

Long-Term Paired Associative Stimulation Enhances Motor ... A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present.