Epidural Stimulation for Spinal Cord Injury

(TSEPI Trial)

Overseen By Manpreet A Chopra, BAMS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Louisville

Disqualifiers: Ventilator, Untreated psychiatric, Nicotine, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses electrical stimulation of the lower spinal cord to help people with severe spinal cord injuries who can't move their legs or stand. The electrical signals aim to reactivate nerves, improving movement and other bodily functions. Electrical stimulation of the spinal cord has been used for pain relief, spasticity control, and movement restoration in spinal cord injury patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an implanted pump or use nicotine, you may not be eligible to participate.

What data supports the effectiveness of the treatment Epidural Stimulation for Spinal Cord Injury?

Research shows that epidural stimulation can help people with spinal cord injuries regain some control over their muscles, allowing them to stand and make step-like movements. In one study, a person with paraplegia was able to stand and control muscle movements after just eight sessions of this treatment. ^{1 2 3 4 5}

Is epidural stimulation safe for humans?

Epidural stimulation has been reported as safe and well-tolerated in patients, with studies showing it can reduce pain and improve function in various conditions. However, there can be specific cases like muscle hypertrophy (enlargement) due to electrode shifts, so monitoring and proper placement are important. ^{2 6 7 8 9}

How is the treatment Epidural Stimulation for Spinal Cord Injury different from other treatments?

Epidural Stimulation is unique because it involves applying electrical stimulation directly to the spinal cord, which can help restore voluntary muscle control and improve standing and walking abilities in people with spinal cord injuries. Unlike other treatments, it directly interacts with the spinal circuits to enhance motor functions, offering a novel approach to rehabilitation. ^{3 5 9 10 11}

Research Team

Susan J Harkema, PhD

Principal Investigator

University of Louisville

Eligibility Criteria

This trial is for adults over 18 with severe spinal cord injury, unable to stand or move legs voluntarily, and experiencing issues like low blood pressure and respiratory dysfunction. They should be at least two years post-injury with stable health but can't join if they use nicotine, have certain implants, untreated conditions, or are pregnant.

Inclusion Criteria

I am 18 years old or older.

My spinal cord injury is not getting worse.

It has been over 2 years since my injury.

Exclusion Criteria

I have not had bladder botox injections in the last year.

You require a machine to help you breathe.

You currently have an untreated mental health disorder or are actively using drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4-6 weeks

Treatment

Participants receive lumbosacral spinal cord epidural stimulation (scES) for cardiovascular function, voluntary movement, or standing with and/or without weight-bearing standing.

12 weeks

Weekly visits for stimulation and training sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of cardiovascular, respiratory, bladder, bowel, and sexual function.

8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term to further assess quality of life and healthcare costs.

Long-term

Treatment Details

Interventions

• Epidural Stimulation
• Stand Training

Trial Overview The study tests how epidural stimulation (scES) helps recover functions affected by spinal cord injuries. Participants will receive scES aimed at improving cardiovascular function, voluntary movement of legs/trunk, or standing ability. The impact on quality of life and healthcare costs will also be evaluated.

Participant Groups

Group I: Voluntary Movement ES + Stand Training Experimental Treatment 1 Intervention

Participants assigned to this group will receive epidural stimulation specific for voluntary movement and will also receive stand training.

Group II: Epidural Stimulation for Voluntary Movement Experimental Treatment 1 Intervention

Participants assigned to this group receive epidural stimulation specifically for voluntary movement.

Group III: Epidural Stimulation for Cardiovascular stability during daily activities Experimental Treatment 1 Intervention

Participants assigned to this arm will receive be randomized to receive epidural stimulation specific for cardiovascular function alone or cardiovascular function and standing, or voluntary movement alone or voluntary movement and standing.

Group IV: Cardiovascular ES + Stand Training Experimental Treatment 1 Intervention

Participants assigned to this group will receive epidural stimulation specific for cardiovascular function and will also receive stand training.

Group V: Acute Epidural Stimulation for Cardiovascular Stability. Experimental Treatment 1 Intervention

Participants are assessed both with and without epidural stimulation for cardiovascular stability for persistent hypotension, orthostatic hypotension and autonomic dysreflexia.

Epidural Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Epidural Stimulation for:

• Spinal cord injury rehabilitation
• Motor function recovery
• Autonomic function recovery

Approved in Canada as Epidural Stimulation for:

• Spinal cord injury rehabilitation
• Motor function recovery
• Autonomic function recovery

Approved in European Union as Epidural Stimulation for:

• Spinal cord injury rehabilitation
• Motor function recovery
• Autonomic function recovery

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Christopher Reeve Paralysis Foundation

Collaborator

Trials

6

Recruited

1,800+

Findings from Research

Spinal cord epidural stimulation (SCES) not only aids in facilitating walking but also improves cardiovascular autonomic regulation and reduces spasticity in a 27-year-old male with a complete spinal cord injury, as shown in assessments conducted 15 weeks apart.

The study demonstrated that SCES can stabilize blood pressure during postural changes and significantly reduce muscle spasticity, suggesting that a single SCES configuration can provide multiple functional benefits, which may enhance its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of percutaneously-implanted epidural stimulation on cardiovascular autonomic function and spasticity after complete spinal cord injury: A case report. Gorgey, AS., Goldsmith, J., Alazzam, A., et al.[2023]

Epidural electrical stimulation (EES) has shown promise in restoring motor functions in two human subjects with complete paralysis due to spinal cord injury, enabling intentional control of step-like activity within just five days after implantation.

The study highlights the effectiveness of using EES-evoked motor responses to guide the precise positioning of electrode arrays during surgery, ensuring stable and targeted stimulation of spinal cord regions associated with lower limb movement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis. Calvert, JS., Grahn, PJ., Strommen, JA., et al.[2020]

Epidural electrical stimulation (EES) of the lumbosacral spinal cord allowed a patient with chronic traumatic paraplegia to achieve significant motor control, including voluntary movement of muscles for specific tasks and rhythmic movements within just 2 weeks of therapy.

This case demonstrates the potential of EES to enable independent standing and controlled movements in patients with severe spinal cord injuries, highlighting its efficacy as a promising intervention for restoring motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia. Grahn, PJ., Lavrov, IA., Sayenko, DG., et al.[2017]

Epidural stimulation (ES) of the lumbosacral spinal cord can selectively activate different leg muscles in individuals with complete motor paralysis, indicating its potential for facilitating movement after spinal cord injuries.

The study, involving three participants, found that the effectiveness of ES in evoking muscle responses depended on stimulation parameters and body weight conditions, suggesting that weight-bearing can reorganize spinal circuitry for improved motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. Sayenko, DG., Angeli, C., Harkema, SJ., et al.[2021]

Spinal cord epidural stimulation (SCES) combined with exoskeletal-assisted walking (EAW) showed promising results in enhancing motor control for a person with complete C7 spinal cord injury, reducing the need for swing assistance from 100% to 35% over 12 weeks.

The approach led to 573 unassisted steps, indicating improved muscle activation and potential for greater independence in movement, suggesting that SCES with EAW could be a practical rehabilitation method for individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The feasibility of using exoskeletal-assisted walking with epidural stimulation: a case report study. Gorgey, AS., Gill, S., Holman, ME., et al.[2021]

Epidural electrical stimulation (EES) has been shown to improve motor function in patients with chronic spinal cord injury, but its effects on paravertebral muscles had not been previously recognized.

In a reported case, hypertrophy of the paravertebral muscles occurred after an electrode shift in a patient with spinal cord injury, suggesting that EES may also influence muscle growth in this area, indicating a potential new avenue for rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertrophy of paravertebral muscles after epidural electrical stimulation shifted: A case report. Li, S., Rong, H., Hao, Z., et al.[2022]

This study will evaluate the effectiveness of EMG-induced rehabilitation treatment in enhancing muscle recovery in 20 patients with spinal cord injury (SCI) who are receiving epidural electrical stimulation, comparing it to conventional rehabilitation methods.

The trial will monitor various outcomes, including muscle strength, quality of life, and safety over a 6-month period, aiming to improve rehabilitation strategies for SCI patients post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury: study protocol for a prospective, randomized, controlled trial. Sun, XP., Shi, JJ., Bao, Y., et al.[2022]

Epidural electrical stimulation of the lumbosacral spinal cord has been shown to improve locomotion and standing in various preclinical models with severe spinal cord injuries, indicating its potential as a therapeutic intervention.

The review highlights that while the stimulation shows promise, the exact mechanisms by which it enhances sensorimotor functions are still not fully understood, which poses challenges for its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury. Audet, J., Lecomte, CG.[2022]

In a study involving seven patients with traumatic paraplegia and chronic pain, six patients reported good to very good outcomes from epidural electrical stimulation over follow-up periods of up to six years.

The positive effects on chronic pain suggest that epidural electrical stimulation should be considered as a treatment option before resorting to more invasive surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with spinal cord stimulation (SCS) in the management of chronic pain in a traumatic transverse lesion syndrome. Buchhaas, U., Koulousakis, A., Nittner, K.[2019]

Epidural spinal electrostimulation (ESES) has shown promising results in improving spinal spasticity and mobility by 20 to 30% in patients with multiple sclerosis and myelopathy, indicating its efficacy in treating severe central motor disturbances.

In addition to mobility improvements, ESES led to a complete disappearance of spastic cramps in all treated cases and significant pain relief in three patients with chronic pain, suggesting its potential as a non-surgical intervention for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. Klingler, D., Kepplinger, B., Gerstenbrand, F., et al.[2006]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of percutaneously-implanted epidural stimulation on cardiovascular autonomic function and spasticity after complete spinal cord injury: A case report. [2023]

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

Electrophysiological Guidance of Epidural Electrode Array Implantation over the Human Lumbosacral Spinal Cord to Enable Motor Function after Chronic Paralysis. [2020]

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

Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia. [2017]

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

Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. [2021]

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

The feasibility of using exoskeletal-assisted walking with epidural stimulation: a case report study. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Hypertrophy of paravertebral muscles after epidural electrical stimulation shifted: A case report. [2022]

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

Epidural spinal electrostimulatory system (ESES) in the management of diabetic foot and peripheral arteriopathies. [2019]

8. India pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury: study protocol for a prospective, randomized, controlled trial. [2022]

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

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Experience with spinal cord stimulation (SCS) in the management of chronic pain in a traumatic transverse lesion syndrome. [2019]

11. Austria pubmed.ncbi.nlm.nih.gov

[Epidural spinal electrostimulation (ESES) in patients with chronic pain and central motor disturbances (author's transl)]. [2006]