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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Many people with partial damages in their spinal cord (iSCI) have physical impairments such as muscle paralysis in legs which make standing balance difficult. Poor balance control often leads to falls, injuries, and hospitalization. Therefore, improvement of standing balance is an important therapeutic goal for these individuals. Our team has shown that a therapy called visual feedback training (VFT) can improve standing balance by allowing individuals with iSCI to actively participate and follow visual feedback of their body sway on a screen like a computer game. We have also found that the application of low-energy electrical pulses to weak muscles called functional electrical stimulation (FES) during VFT can enhance the training effects. Recently, transcutaneous spinal cord stimulation (TSCS) has been discussed as a promising technique to further promote the rehabilitation effects after SCI by enhancing the connectivity between the brain and spinal cord and within the spinal pathways. However, to date, the potential of combining the two techniques (TSCS+FES) to improve the standing balance remains unknown. 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 muscles during VFT on the functional and neurophysiological outcomes in individuals living with iSCI. Participants will be randomly allocated to receive combined TSCS with FES or FES alone during VFT for 12 training sessions over 4 weeks. We expect that the new therapy would further improve balance and strengthen the neural connections between the brain and muscles. The expected changes in the neural connections will be measured by recording electrical signals from the lower limb muscles following stimulation of the motor region of the brain. Results of this study will be used for a larger-scale study in people with iSCI to improve balance and reduce falls during their daily life activities.

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 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 with spinal cord injuries. These methods have been beneficial in other conditions like Parkinson's Disease and chronic pain, suggesting potential for spinal cord injury treatment. ^{1 2 3 4 5}

Is Combined Neuromodulation Therapy generally safe for humans?

Combined Neuromodulation Therapy, including spinal cord stimulation, has been shown to be relatively safe with low rates of serious complications. For example, a study on cervical spinal cord stimulation reported a 0.5% rate of spinal cord injury and no deaths, although there are risks of complications like infection and device issues. ^{1 2 6 7 8}

How is Combined Neuromodulation Therapy different from other treatments for spinal cord injury?

Combined Neuromodulation Therapy is unique because it integrates multiple neuromodulation techniques, such as epidural stimulation and deep brain stimulation, to enhance movement and recovery after spinal cord injury. This approach aims to improve the effectiveness of treatment by activating different parts of the nervous system, which is not typically done with standard treatments. ^{1 2 4 9 10}

Research Team

Kei Masani, PhD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Combined neuromodulatory approaches in the central nervous system for treatment of spinal cord injury. [2023]

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

Utilizing Neuromodulation in the Treatment of Spinal Cord Injury: An Assessment of Clinical Trials from the National ClinicalTrials.gov Database. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Noninvasive neuromodulation and rehabilitation to promote functional restoration in persons with spinal cord injury. [2023]

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

Brain-Computer Interface, Neuromodulation, and Neurorehabilitation Strategies for Spinal Cord Injury. [2021]

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

Pharmacologic Management of Acute Spinal Cord Injury. [2017]

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

Rate of perioperative neurological complications after surgery for cervical spinal cord stimulation. [2017]

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

Spinal Cord Stimulator Implant Infection Rates and Risk Factors: A Multicenter Retrospective Study. [2022]

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

Neuromodulation. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. Korea (South) pubmed.ncbi.nlm.nih.gov

A Gene and Neural Stem Cell Therapy Platform Based on Neuronal Cell Type-Inducible Gene Overexpression. [2018]