Non-Invasive Neuromodulation for Spinal Cord Injury

(RISES-T2 Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Thomas Jefferson University

Disqualifiers: Cardiopulmonary disease, Mood disorders, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The objectives of this study are to (1) determine the effects of neuromodulation techniques on mobility in persons with chronic SCI, as measured by subjective and objective measures, and (2) to determine the optimal combination of techniques that modify mobility and movement in an individual. The neuromodulation techniques explored will be methods of electromagnetic stimulation - that is, electrical stimulation and magnetic stimulation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment RISES-T System for spinal cord injury?

Research shows that non-invasive electrical stimulation can help people with spinal cord injuries regain some voluntary movement. In one study, electrical stimulation combined with training improved movement in all participants, and another study found that similar stimulation methods helped improve arm and hand function. ^{1 2 3 4 5}

Is non-invasive neuromodulation for spinal cord injury safe for humans?

Non-invasive spinal cord stimulation methods are generally considered safe, as they are perceived to offer improved safety and patient acceptance compared to invasive methods. Studies in animals, such as rats and dogs, have shown that these methods are tolerable and safe, even with repeated treatments. ^{2 6 7 8 9}

How does the non-invasive neuromodulation treatment for spinal cord injury differ from other treatments?

This treatment is unique because it uses painless electrical stimulation on the skin to reactivate and train the spinal cord's motor networks, allowing for recovery of voluntary movement even in cases of long-term paralysis. Unlike traditional methods, it combines electrical stimulation with pharmacological strategies and intensive rehabilitation, offering a non-invasive and potentially more effective approach to restoring movement. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for individuals with chronic spinal cord injury or disease, at least a year post-injury, who can engage in therapy and have caregiver support. They must be able to consent and participate in recorded sessions. Those with severe medical conditions, uncontrolled symptoms, skin issues where electrodes attach, active implants like pacemakers, or are pregnant/breastfeeding cannot join.

Inclusion Criteria

My spinal injury is classified between A and D on the ASIA scale.

I can take part in physical and occupational therapy programs.

Is willing to undergo audio-visual recording sessions

Exclusion Criteria

Is not a candidate for other reason determined by the investigators

I do not have any severe health issues that could affect the study.

I have skin damage where electrodes would be placed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1 - Assessment Sessions

Determine which muscles respond to stimulation and establish parameters for Part 2

4 weeks

Multiple visits for baseline assessments and parameter setting

Part 2 - Experimental Cycles

Intervention sessions with transcutaneous stimulation and biometric assessments

Up to 22 weeks

Regular visits for intervention and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• RISES-T System

Trial Overview The RISES-T System is being tested to see how non-invasive electrical and magnetic neuromodulation techniques affect mobility in people with chronic spinal injuries. The study aims to find the best combination of these techniques to improve movement.

Participant Groups

Group I: Experimental Treatment Arm Experimental Treatment 1 Intervention

Participants will receive closed-loop transcutaneous spinal cord stimulation via the RISES-T System while completing repetitive task practice

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Tim Reynolds

Collaborator

Trials

1

Recruited

10+

Findings from Research

A novel noninvasive stimulation strategy combined with pharmacological intervention successfully re-engaged spinal locomotor networks in individuals with motor complete paralysis, enabling locomotor-like stepping without voluntary effort during a single session.

After 18 weeks of treatment, all five subjects showed significant improvements in voluntary motor control, with evidence of re-established functional connectivity between the brain and spinal cord, allowing for selective muscle activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Reactivation of Motor Descending Control after Paralysis. Gerasimenko, YP., Lu, DC., Modaber, M., et al.[2018]

Spinal cord stimulation (SCS) is evolving from a treatment for intractable pain to a potential method for restoring function after spinal cord injuries, driven by advances in understanding spinal cord lesions and compensatory mechanisms.

New SCS strategies, like spatiotemporal neuromodulation, show promise but require intensive rehabilitation techniques to be effective, highlighting the need for well-designed clinical trials to evaluate safety and efficacy in real-world applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks. Pradat, PF., Hayon, D., Blancho, S., et al.[2023]

In a proof-of-concept study involving three adults with cervical spinal cord injury, repetitive QuadroPulse transcranial magnetic stimulation (rTMS(QP)) showed functional benefits, particularly in improving walking speed and cortical excitability without any adverse effects.

The combination of rTMS(QP) with targeted exercises led to even greater improvements in motor function, suggesting that this approach could be effective and warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies. Alexeeva, N., Calancie, B.[2018]

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]

In a study involving 122 participants with chronic low back and/or leg pain, multiphase spinal cord stimulation (SCS) significantly reduced pain levels, with mean reductions of -4.3 and -4.7 on the numerical rating scale for two different multiphase therapies.

The multiphase SCS therapies were found to be safe, with only one non-serious device-related adverse event reported and no infections, suggesting a favorable safety profile for this new stimulation paradigm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. Kapural, L., Patterson, DG., Li, S., et al.[2023]

A new animal model for transcutaneous spinal cord stimulation (tSCS) was developed, which accurately mimics human responses and allows for stable, repeated treatments after spinal cord injury (SCI) with minimal restraint.

The study demonstrated that tSCS can effectively modulate motor output in rats after complete spinal cord transection, suggesting its potential for promoting neuroplasticity and functional recovery in SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapting Human-Based Transcutaneous Spinal Cord Stimulation to Develop a Clinically Relevant Animal Model. Malloy, DC., Knikou, M., Côté, MP.[2023]

Transdermal micropolarization using local direct currents improved motor and autonomic functions in patients with spinal cord trauma and tuberculous spondylitis, indicating its potential as a therapeutic intervention.

The study monitored clinical and electrophysiological changes, suggesting that direct currents can positively affect the functional state of the spinal cord and heart activity, highlighting the mechanism of action for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of micropolarization in the treatment of spinal cord lesions. Shelyakin, AM., Preobrazhenskaya, IG., Komantsev, VN., et al.[2019]

Electrochemical neuromodulation therapies and robot-assisted rehabilitation have shown promise in restoring voluntary leg movements in chronic paraplegic individuals, indicating potential for improving mobility after spinal cord injuries.

In rodent models, these therapies led to significant remodeling of neural pathways, suggesting that similar mechanisms may be effective in humans, although challenges remain in translating these findings into widespread clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury. van den Brand, R., Mignardot, JB., von Zitzewitz, J., et al.[2018]

References

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

Noninvasive Reactivation of Motor Descending Control after Paralysis. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks. [2023]

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

Retraction of "Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Motor and Gait Improvement in Incomplete Spinal Cord Injury Patients". [2019]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies. [2018]

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

Cortical and Subcortical Effects of Transcutaneous Spinal Cord Stimulation in Humans with Tetraplegia. [2021]

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

Effect of alternating current stimulation of the spinal cord on recovery from acute spinal cord injury in rats. [2019]

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

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. [2023]

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

An imposed oscillating electrical field improves the recovery of function in neurologically complete paraplegic dogs. [2013]

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

Adapting Human-Based Transcutaneous Spinal Cord Stimulation to Develop a Clinically Relevant Animal Model. [2023]

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

The use of micropolarization in the treatment of spinal cord lesions. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Neuroprosthetic technologies to augment the impact of neurorehabilitation after spinal cord injury. [2018]

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

Reversing 21 years of chronic paralysis via non-invasive spinal cord neuromodulation: a case study. [2021]