Combined Neuromodulation Therapy for Spinal Cord Injury

Overseen By Shirin Tajalli, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Severe spasticity, Contractures, Epilepsy, others

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

Compensation: Varies

Number of Visits: 12

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two therapies can improve standing balance for individuals with partially damaged spinal cords (iSCI). It examines whether adding transcutaneous spinal cord stimulation (TSCS), which enhances brain and spinal cord connections, to functional electrical stimulation (FES) during visual feedback training (similar to a computer game) makes a difference. Participants will receive either both TSCS and FES or just FES while performing these exercises. The trial seeks individuals who have had a stable spinal cord injury for over a year and experience balance difficulties, excluding those with conditions like vision loss or severe muscle stiffness. As an unphased trial, this study offers a unique opportunity to explore innovative therapies that could enhance quality of life.

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 prior data suggests that this combined neuromodulation therapy is safe for individuals with spinal cord injury?

Research has shown that combining two methods, TSCS and FES, is generally safe for people with spinal cord injuries. TSCS uses electrical stimulation on the spine, and studies have found it safe and practical during training. In one study, seven people with spinal cord injuries safely used TSCS along with other training. Another review found that electrical stimulation methods like TSCS and FES (which helps muscles move) are safe and effective for improving movement in people with long-term spinal cord injuries. These methods have been used before and are considered well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Combined Neuromodulation Therapy for spinal cord injury because it offers a novel approach by combining Functional Electrical Stimulation (FES) and Transcutaneous Spinal Cord Stimulation (TSCS). Unlike traditional treatments that mainly focus on rehabilitation exercises or medications to manage symptoms, this approach directly targets neural pathways to enhance motor function. The FES+TSCS group uses a unique combination of open-loop and closed-loop systems to stimulate multiple muscles and provide real-time visual feedback, potentially improving motor control and sensory feedback. By offering a more dynamic and interactive way to engage the nervous system, this therapy could lead to significant improvements in mobility and quality of life for patients with spinal cord injuries.

What evidence suggests that this trial's treatments could be effective for improving standing balance in individuals with iSCI?

Research shows that transcutaneous spinal cord stimulation (TSCS), when combined with other treatments, can aid recovery from spinal cord injuries. In this trial, one group will receive a combined neuromodulation therapy using TSCS and functional electrical stimulation (FES) during visual feedback training (VFT). Studies have found that TSCS, when paired with activity-based training (ABT), improves function in those with long-term spinal injuries, particularly by enhancing muscle strength and movement. FES boosts muscle activity by sending electrical signals to weak muscles. Using TSCS and FES together during VFT is expected to further improve standing balance by strengthening the connection between the brain and muscles. This combined approach has shown promise in past research, suggesting it could effectively improve balance in people with spinal cord injuries. ^{1 2 6 7 8}

Who Is on the Research Team?

Kei Masani, PhD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 18 with partial spinal cord injury (iSCI) who have muscle paralysis affecting balance but no other conditions impacting walking or balance. They must be at least one year post-injury, not pregnant, free from epilepsy, and without severe spasticity or nerve damage in the legs.

Inclusion Criteria

My balance and mobility score is less than 46.

I don't have any conditions besides SCI affecting my walking or balance.

My spinal cord injury is moderate to mild (AIS C or D).

Exclusion Criteria

My legs do not respond to electrical stimulation due to nerve damage.

I don't have conditions like a pacemaker, active cancer, recent radiation, epilepsy, or skin issues that would prevent electrical stimulation.

I cannot straighten my legs or hips fully due to stiffness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either combined TSCS with FES or FES alone during VFT for 12 training sessions over 4 weeks

4 weeks

12 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Combined Neuromodulation Therapy

Trial Overview The study tests a new therapy combining visual feedback training (VFT), functional electrical stimulation (FES) of ankle muscles, and transcutaneous spinal cord stimulation (TSCS). Participants will either receive TSCS+FES during VFT or just FES during VFT across 12 sessions to improve balance and neural connections.

How Is the Trial Designed?

Group I: FES+TSCS (combined) neuromodulation group Experimental Treatment 1 Intervention

For the combined neuromodulation with VFT group, the sub-motor threshold, open-loop TSCS will be coupled with closed-loop FES of ankle muscles during VFT. For this purpose, 2 electrical stimulators, one for each leg will stimulate SOL and TA muscles bilaterally while open-loop tonic lumbar TSCS will be applied at an intensity producing paresthesia in most of the lower-limb dermatomes

Group II: FES group Active Control 1 Intervention

For the FES with VFT group, participants will receive visual feedback regarding their center of pressure location during four games with varying levels of difficulty and FES will be applied bilaterally to SOL and TA via a closed-loop system.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Combining epidural stimulation (ES) with deep brain stimulation (DBS) shows promise in enhancing movement recovery after spinal cord injury (SCI), as it targets both spinal and brain circuits to improve motor function.

Recent studies suggest that DBS of the mesencephalic locomotor region could significantly boost the effectiveness of neuromodulation therapies, indicating a potential new clinical approach for restoring locomotion in individuals with severe SCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined neuromodulatory approaches in the central nervous system for treatment of spinal cord injury. Noga, BR., Guest, JD.[2023]

Spinal cord stimulation is a key treatment for chronic neuropathic pain, serving as a neuromodulation therapy that can help manage pain symptoms effectively.

The article outlines the criteria for determining which patients are suitable for spinal cord stimulation therapy, ensuring that the right individuals receive this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation. Love-Jones, S.[2021]

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]

In a study analyzing 2053 cases of cervical spinal cord stimulation (cSCS) from 2002 to 2011, the rate of spinal cord injury was found to be 0.5%, which is higher than previously reported, indicating a need for careful patient selection and counseling.

Despite the spinal cord injury rate, cSCS remains a relatively safe procedure with low rates of other complications (1.1% neurological, 1.4% medical, and 11.7% general perioperative complications), making it a viable option for pain management in patients, especially in an aging population reliant on opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of perioperative neurological complications after surgery for cervical spinal cord stimulation. Chan, AK., Winkler, EA., Jacques, L.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39998450

Safety and Effectiveness of Multisite Transcutaneous ... Combined tSCS + ABT facilitated functional recovery after chronic SCI. Improvements required ≥60 tSCS-ABT sessions, with further exposure to tSCS facilitating ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925000078

Safety and Effectiveness of Multisite Transcutaneous ... This study showed that tSCS combined with ABT is safe, feasible, and effective in adults with chronic SCI ranging from the cervical to thoracic level when ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05940636

A Novel Combined Neuromodulation Therapy to Enhance ... In this study, through the completion of a clinical trial, we will investigate the effects of an intervention that combines lumbar TSCS with FES of ankle ...

4. jneuroengrehab.biomedcentral.com jneuroengrehab.biomedcentral.com/articles/10.1186/s12984-025-01545-8

Transcutaneous spinal cord stimulation combined with robotic ... The outcomes of this study suggest that the combination of standard Lokomat training with tSCS for 20 sessions was effective for LEMS and gait recovery in ...

5. withpower.com withpower.com/trial/phase-spinal-cord-injuries-8-2023-b0738

Combined Neuromodulation Therapy for Spinal Cord Injury Research shows that combining different neuromodulation techniques, like epidural stimulation and deep brain stimulation, can help improve movement in people ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11214755/

Electrical Stimulation and Motor Function Rehabilitation in ... This review outlines the various ways electrical stimulation techniques can aid in the motor recovery of SCI patients.

7. frontiersin.org frontiersin.org/journals/rehabilitation-sciences/articles/10.3389/fresc.2021.740307/full

Transcutaneous Electrical Spinal Cord Stimulation to ... Augmenting UE and LE training using TSCS in the clinical setting was shown to be safe and feasible in seven individuals with SCI who had already ...

8. e-neurospine.org e-neurospine.org/journal/view.php?doi=10.14245/ns.2244652.326

A Review of Functional Restoration From Spinal Cord ... This review indicates that eSCS and tSCS are efficacious and safe treatments for chronic SCI, with the potential to improve motor and autonomic ...