Epidural Stimulation + Training for Spinal Cord Injury

(MC-PP-3 Trial)

Recruiting at 1 trial location

Overseen By Leighann Martinez

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Susan Harkema PhD

Must not be taking: Anti-spasticity, Botox

Disqualifiers: Ventilator dependence, Untreated psychiatric disorder, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 10

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether epidural stimulation can help people with spinal cord injuries improve their ability to stand, walk, and manage bladder function. Researchers are testing various combinations of epidural stimulation with training focused on bladder capacity, bladder voiding, standing, and stepping. This trial may suit individuals with a stable medical condition who cannot stand or move their legs independently and have bladder issues due to a spinal cord injury between the T1 and T10 vertebrae. As an unphased trial, participants can contribute to groundbreaking research that could lead to new treatments for spinal cord injuries.

Will I have to stop taking my current medications?

The trial requires that participants are not on any current anti-spasticity medication regimen and must not have received botox injections in the prior six months. Other medications are not specified, so it's best to discuss with the trial team.

What prior data suggests that this method is safe for improving movement and bladder function in individuals with spinal cord injury?

Research has shown that epidural electrical stimulation (EES) has been safely used in studies for spinal cord injuries. In animal studies, this stimulation helped animals regain movement. Recent studies with people also show that EES can improve movement and function in the legs after a spinal cord injury.

Regarding safety, EES has been well-tolerated in both human and animal studies. These studies have not reported major side effects, indicating that the treatment is generally safe. While some risk exists with medical treatments, the evidence so far suggests that EES can be used without major safety concerns.

For those considering joining a clinical trial with EES, this information may provide confidence in its safety. It is important to discuss any concerns with the researchers or a doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine epidural stimulation with specific training exercises to potentially improve mobility and bladder function in individuals with spinal cord injuries. Unlike standard treatments, which typically focus on rehabilitation through physical therapy alone, this approach integrates electrical stimulation directly to the spinal cord to enhance neural recovery. The unique combination of epidural stimulation with targeted training—like bladder capacity and voiding efficiency training, as well as stand and step training—offers a novel way to address both locomotion and bladder control, which are often challenging to manage with current methods. This innovative strategy aims to provide a more holistic improvement in quality of life for those affected by spinal cord injuries.

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

Studies have shown that epidural stimulation can help people with spinal cord injuries improve bladder control and reduce urinary incontinence. In this trial, some participants will receive epidural stimulation combined with bladder capacity or voiding efficiency training. For those concerned about mobility, research indicates that combining epidural stimulation with specialized movement training can restore the ability to stand and walk. This trial will also test epidural stimulation with stand or step training. These findings suggest that epidural stimulation might effectively improve both bladder function and movement after a spinal cord injury. Overall, combining this stimulation with targeted training shows promising results in helping individuals regain important functions. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a stable, non-progressive spinal cord injury (SCI) between T1 and T10. They must be within one year post-injury, unable to stand or walk independently, have bladder dysfunction due to SCI, and not on anti-spasticity meds or received botox in the last six months. Excluded are those ventilator-dependent, with untreated major health issues or psychiatric disorders/drug abuse.

Inclusion Criteria

Your injury occurred no more than 1 year ago.

I cannot move all the joints in my legs on my own.

I have not had any botox injections in the last six months.

Exclusion Criteria

I have heart, lung, bladder, or kidney conditions not caused by my spinal cord injury.

Pregnant at the time of enrollment or planning to become pregnant during the time course of the study

You have a mental health condition that has not been treated, or you are currently abusing drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bladder Training

Participants receive 80 sessions of bladder training with epidural stimulation

3 months

5 visits per week

Locomotor Training

Participants receive 160 locomotor training sessions with epidural stimulation

6 months

5 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Epidural stimulation + Bladder Capacity Training
• Epidural stimulation + Bladder Voiding Efficiency Training
• Epidural stimulation + Stand Training
• Epidural stimulation + Step Training

Trial Overview

The study tests if epidural stimulation can improve standing, walking, and bladder functions in people with acute SCI. Participants will undergo different training protocols: Bladder Capacity Training, Bladder Voiding Efficiency Training, Step Training or Stand Training alongside the epidural stimulation.

How Is the Trial Designed?

Group I: Locomotion Experimental Treatment 2 Interventions

Participants will receive 160 locomotor training sessions with epidural stimulation. These sessions may occur once a day (stand and step will alternate days) or twice a day (stand and step on the same day) as recommended by the study physician. Participants will train 5 days per week and each session will last between 1 to 1.5 hours.

Group II: Bladder+Locomotion Experimental Treatment 4 Interventions

Participants will receive 80 sessions of bladder training alone followed by 80 sessions of locomotor training sessions with epidural stimulation. They will be asked to continue with your bladder training once you start locomotor training. Locomotor Training sessions may occur once a day (stand and step will alternate days) or twice a day (stand and step on the same day) as recommended by the study physician. Participants will train 5 days per week and each session will last between 1 to 1.5 hours.

Epidural stimulation + Bladder Capacity Training 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
• Bladder dysfunction management
• Motor function improvement

Approved in Canada as Spinal Cord Epidural Stimulation for:

• Spinal cord injury rehabilitation
• Chronic pain management

Approved in European Union as Epidural Electrical Stimulation for:

• Spinal cord injury rehabilitation
• Motor function improvement
• Autonomic function management

Who Is Running the Clinical Trial?

Susan Harkema PhD

Lead Sponsor

Trials

2

Recruited

30+

Claudia Angeli

Lead Sponsor

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Sacral spinal cord stimulation (SCS) effectively activates nerves that control the bladder and urethra, demonstrating its potential to improve lower urinary tract functions.

The use of a high-density electrode array allowed for selective recruitment of specific nerves, indicating a targeted approach that could help restore bladder and urethral function after injuries or diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-density spinal cord stimulation selectively activates lower urinary tract nerves. Jantz, MK., Gopinath, C., Kumar, R., et al.[2023]

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 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]

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]

Epidural electrical stimulation (EES) combined with task-specific training may negatively affect bladder function in individuals with spinal cord injury, as one participant experienced increased urinary incontinence and worsening bladder compliance after 12 months of EES training.

On a positive note, EES appears to enhance body composition, as one participant gained 9.1 kg of lean mass and improved fat distribution, suggesting that EES can be beneficial for muscle activation and body composition in individuals with chronic paralysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of long-term epidural electrical stimulation enabled task-specific training on secondary conditions of chronic paraplegia in two humans. Beck, L., Veith, D., Linde, M., et al.[2021]

Spinal cord epidural stimulation (scES) has shown promise in improving bladder control in individuals with chronic, motor complete spinal cord injury, as demonstrated in a study involving one participant over four months and later confirmed in four additional participants.

The optimal stimulation frequency for enhancing reflexive bladder emptying was identified as 30 Hz, indicating that scES can effectively reduce post-void residual volumes and improve urological function after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury. Herrity, AN., Williams, CS., Angeli, CA., et al.[2019]

Surface and minimally invasive electrical stimulation techniques can effectively manage bladder function in spinal cord injured patients, showing similar urodynamic responses to traditional implanted electrodes.

Specific parameters for effective daily voiding using sacral surface electrodes were identified, including 10 pulses per second, 30 to 45 milliamps, and a pulse duration of 0.6 milliseconds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surface stimulation techniques for bladder management in the spinal dog. Walter, JS., Wheeler, JS., Robinson, CJ., et al.[2019]

Citations

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These results demonstrate the safety and efficacy of ARC EX Therapy to improve hand and arm functions in people living with cervical SCI.

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EES works by implanting electrodes into the epidural space of the spinal cord to deliver electrical stimulation to neural circuits below the ...