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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how epidural stimulation can help individuals with severe spinal cord injuries regain functions such as voluntary movement, standing, and autonomic nervous system improvement, which affects heart rate and blood pressure. Participants are divided into groups to test different aspects of epidural stimulation, including cardiovascular stability and voluntary movement enhancement. Individuals who have had a spinal cord injury for at least two years and experience challenges like difficulty moving their legs, standing, or cardiovascular issues such as low blood pressure may be suitable candidates for this study. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially improve 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. However, if you have an implanted pump or use nicotine, you may not be eligible to participate.

What prior data suggests that epidural stimulation is safe for spinal cord injury recovery?

Research has shown that epidural electrical stimulation (EES) is generally safe for people with spinal cord injuries. Studies have found that using EES with physical therapy can help restore movement and sensation. These studies have not shown strong evidence of serious side effects, suggesting EES is safe.

Early studies have found stand training to be safe for people with spinal cord injuries. Participants in these studies did not experience major side effects.

In summary, current research suggests that both epidural stimulation and stand training are safe for people with spinal cord injuries. These treatments are generally well-tolerated and show promise in improving movement and balance. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about epidural stimulation for spinal cord injury because it offers a new approach to improving cardiovascular stability and voluntary movement in affected individuals. Unlike traditional treatments that primarily focus on physical therapy and medications to manage symptoms, epidural stimulation directly targets the spinal cord to enhance nerve activity. This method has the potential to improve cardiovascular function and enable voluntary movements, which could significantly enhance quality of life. Additionally, combining this stimulation with stand training aims to further support physical function and stability. Overall, this innovative approach could lead to more effective and comprehensive management of spinal cord injury symptoms.

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

Research has shown that epidural stimulation, one of the treatments in this trial, can benefit people with severe spinal cord injuries in several ways. Studies have found that this treatment can restore some voluntary movement, allowing individuals to regain control over their legs and upper body. It can also improve heart and blood circulation, stabilizing blood pressure and enhancing overall heart function. These findings suggest that epidural stimulation could enhance the quality of life for those with severe spinal cord injuries. Participants in this trial will be assigned to different arms to assess the effects of epidural stimulation on cardiovascular stability, voluntary movement, or a combination with stand training. ^{3 6 7 8 9}

Who Is on the Research Team?

Susan J Harkema, PhD

Principal Investigator

University of Louisville

Are You a Good Fit for This Trial?

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

My spinal cord injury is not getting worse.

It has been over 2 years since my injury.

My health condition is stable.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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 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 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 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 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]

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]

Citations

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A case study of percutaneous epidural stimulation to enable motor control in two men after spinal cord injury. Ashraf S. Gorgey ...