Non-Invasive Stimulation for Spinal Cord Injury

Overseen By Zoe Tsagaris, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kathleen Friel

Disqualifiers: Complete lesion, Non-traumatic lesion, Unstable condition, Neurological illness, others

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: 7

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to help people with spinal cord injuries regain movement. It uses non-invasive stimulation techniques to determine if they can enhance spinal cord activity and improve motor function. The trial includes three groups, each receiving a slightly different version of the stimulation to compare results. Individuals with a spinal cord injury from a traumatic event, who retain some movement in their ankle muscles, might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What prior data suggests that this technique is safe for spinal cord injury patients?

Research has shown that non-invasive treatments for spinal cord injuries are generally safe. In previous studies, patients tolerated these treatments well. Specifically, non-invasive brain stimulation has helped improve movement in people with spinal cord injuries. While results can vary, these treatments are considered safe for most people.

Additionally, other studies have found improvements in skills like hand strength and grip. This indicates that the treatment not only aims to be effective but is also generally safe. Remember, this information is based on earlier studies, and ensuring safety remains a top priority in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the non-invasive stimulation technique for spinal cord injury because it offers a novel approach to treatment without the need for surgery or drugs. Unlike traditional treatments, which often involve medications or surgical interventions, this method uses transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation to potentially enhance nerve function. The unique timing of the stimulation—delivered 0ms, 20ms, or 50ms before the nerve stimulus—might optimize nerve signaling and improve motor function. This approach could minimize side effects and provide a less invasive option for patients, making it a promising area of exploration in spinal cord injury rehabilitation.

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

Research has shown that non-invasive stimulation can enhance movement in people with spinal cord injuries. In this trial, participants will receive various forms of paired stimulation, using magnetic or electrical pulses to improve nerve communication. One study found that 72% of participants achieved or exceeded their expected improvements in arm and hand function. Other studies have found that combining this type of stimulation with activities like cycling can improve movement and walking in individuals with partial spinal cord injuries. Early results are promising, with noted improvements in both strength and movement. ^{1 2 5 6 7}

Who Is on the Research Team?

Kathleen Friel, PhD

Principal Investigator

Burke Medical Research Institute

Are You a Good Fit for This Trial?

This trial is for individuals with chronic spinal cord injuries (more than 6 months old) who still have some motor function in their ankle muscles. Participants must have an incomplete lesion as classified by the ASIA Impairment Scale and a traumatic cause for their injury.

Inclusion Criteria

My spinal cord injury is partially impairing my movement.

My leg injury was caused by trauma and I can still move my ankle a little (LEMS≥3).

My spinal cord injury is older than 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo paired stimulation (SAS) with subthreshold TMS and peripheral nerve stimulus for 15 minutes per session

1 week

5 sessions (in-person)

Follow-up

Participants are monitored for changes in spinal excitability and motor function

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Non-Invasive Stimulation

Trial Overview The study is testing Spinal Associative Stimulation (SAS), which combines Transcranial Magnetic Stimulation (TMS) with Peripheral Nerve Stimulation to see if it can increase spinal excitability and improve motor recovery in participants.

How Is the Trial Designed?

Group I: SAS20 Experimental Treatment 1 Intervention

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 20ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Group II: SAS0 Active Control 1 Intervention

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 0ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Group III: SAS50 Active Control 1 Intervention

The paired stimulation (SAS) will be comprised of patient adjusted subthreshold TMS (80% of resting motor threshold over optimal site for soleus muscle), delivered 50ms prior to a peripheral nerve stimulus in the popliteal fossa and will be repeated at 0.1 Hz for 15 minutes (90 stimuli pairs).

Who Is Running the Clinical Trial?

Kathleen Friel

Lead Sponsor

Trials

3

Recruited

90+

Burke Medical Research Institute

Collaborator

Trials

24

Recruited

1,500+

Published Research Related to This Trial

Transcutaneous spinal cord stimulation (tSCS) shows potential for generating motor activity in individuals with spinal cord injury, but the overall quality of the studies reviewed was poor-to-fair, indicating a need for more rigorous research.

The review identified significant variability in stimulation parameters and outcome measurements across the 25 studies analyzed, highlighting the necessity for standardized methods to improve the reliability and comparability of tSCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. Taylor, C., McHugh, C., Mockler, D., et al.[2022]

Continuous electrical stimulation of the spinal cord at intensities greater than 10 mA for 30 minutes can cause permanent damage, including changes in spinal cord evoked potentials and tissue necrosis.

Intermittent stimulation at 10 mA with 1-minute resting intervals appears to be safe, as no spinal cord lesions were observed, suggesting a safer approach for spinal cord monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of epidural electrical stimulation modalities on spinal cord function and morphology in cats. Takakuwa, K., Tsuji, H., Takano, H., et al.[2013]

Transcutaneous electrical spinal cord stimulation combined with physical therapy led to significant improvements in upper extremity function for a 62-year-old male with a chronic incomplete spinal cord injury, including a 52-point increase in strength and sensation scores after four weeks of treatment.

Remarkably, the functional gains achieved persisted for over three months after the treatment ended, indicating that this noninvasive approach can promote lasting neuroplasticity and recovery in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. Inanici, F., Samejima, S., Gad, P., et al.[2020]

Only 30% of the 40 reviewed clinical trials on acute spinal cord injury provided satisfactory reporting of adverse events, indicating a significant gap in safety information that is crucial for assessing risk and designing future studies.

A staggering 82.5% of trials failed to report laboratory-defined toxicity satisfactorily, highlighting the need for improved standards in safety reporting to ensure comprehensive understanding of treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Safety Reporting in Acute Spinal Cord Injury Clinical Trials: Challenges and Recommendations. Aspinall, P., Harrison, L., Scheuren, P., et al.[2023]

In a study of 69 patients with implanted spinal cord stimulators (SCSs) who underwent 78 MRI scans, the overall adverse event rate for off-label MRI use was low at 9.72%, with no serious adverse events reported.

All reported clinical adverse events were minor and resolved, suggesting that the benefits of MRI for pain management in patients with older SCS models may outweigh the associated risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Magnetic Resonance Imaging (MRI) in Patients with Persistent Pain with Spinal Cord Stimulators: A Case Series. Ragukonis, T.[2022]

In a study of 68 patients who had spinal cord stimulation paddle electrodes removed, the most common reason for removal was loss of coverage or effect (75%), indicating that while SCS is effective, it may not always provide lasting relief.

Postoperative complications occurred in 11.75% of patients, with two major complications requiring reoperation, highlighting that while SCS removal is generally safe, it does carry some risks that patients should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. Maldonado-Naranjo, AL., Frizon, LA., Sabharwal, NC., et al.[2022]

In a study of 8326 patients who underwent spinal cord stimulation (SCS) implantation, the overall incidence of spinal cord injury (SCI) was found to be low at 2.13%, indicating that SCS is a generally safe procedure.

There was no significant difference in the rates of SCI or spinal hematoma between patients receiving percutaneous (2.35%) and paddle (1.71%) electrode implantation, suggesting similar safety profiles for both methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. Petraglia, FW., Farber, SH., Gramer, R., et al.[2022]

Electrical stimulation significantly enhances the proliferation and differentiation of spinal cord-derived neural stem/progenitor cells (SC-NSPCs) in both in vitro and in vivo rodent models of spinal cord injury (SCI), leading to improved functional recovery.

The mechanism behind these benefits appears to involve the activation of the Wnt/β-catenin signaling pathway, suggesting that electrical stimulation could be a promising noninvasive treatment strategy for promoting neural regeneration after SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study. Bang, WS., Han, I., Mun, SA., et al.[2023]

A multicenter randomized clinical trial is investigating the effectiveness of combining spinal cord transcutaneous stimulation (scTS) with activity-based training (ABT) for improving upper extremity function in individuals with cervical spinal cord injury, showing promising preliminary results.

In a small sample of four participants, the combination of scTS and ABT led to immediate and sustained improvements in upper extremity function, with one participant experiencing a remarkable 5-fold increase in function, indicating potential for significant rehabilitation benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Spinal Cord Transcutaneous Stimulation with Activity-based Training to Improve Upper Extremity Function Following Cervical Spinal Cord Injury. Zhang, F., Carnahan, J., Ravi, M., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11887137/

Non-invasive cerebral and spinal cord stimulation for motor ... In this review we aim to compare the effect of non-invasive cerebral and spinal cord stimulation on gait recovery and motor strength of lower limbs in subjects ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772529425000530

nTMS in spinal cord injury: Current evidence, challenges ... nTMS has shown encouraging preliminary results in both clinical assessment and rehabilitation (motor and pain) of patients with SCI.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05975606

Non-invasive Brain Stimulation Paired With FES Cycling ... Motor and gait improvement in patients with incomplete spinal cord injury induced by high-frequency repetitive transcranial magnetic stimulation. Top Spinal ...

4. nature.com nature.com/articles/s41591-024-02940-9

Non-invasive spinal cord electrical stimulation for arm and ... Of the 60 participants included in the primary effectiveness endpoint analysis, 43 (72%) met or exceeded the minimally important difference (MID) ...

5. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-023-01129-4

Effects of non-invasive brain stimulation on motor function ... NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9837916/

Effects of non-invasive brain stimulation on motor function ... NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06867809

NCT06867809 | Spine and Brain Stimulation for Movement ... Stimulation of the spinal cord and brain represents a new experimental therapy that may have potential to restore movement after spinal cord injury.