Epidural Stimulation + Training for Spinal Cord Injury

(MC-PP-3 Trial)

Overseen By Manpreet Chopra

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

Trial Summary

What is the purpose of this trial?

The loss of movement and walking ability significantly affects quality of life after spinal cord injury. In addition, bladder dysfunction consistently ranks as one of the top disorders affecting quality of life after spinal cord injury. The overall objective of this study is to demonstrate that epidural stimulation may be a method for improving stepping, standing and bladder function in individuals with spinal cord injury. With the use of epidural stimulation, the investigators propose to investigate how well the participant can stand and walk and how well the participant's bladder can store or hold urine as well as void or empty urine. The results of this study may aid in the development of treatments to help individuals with spinal cord injuries that are unable to stand or walk and have impaired bladder function.

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

Research shows that spinal cord epidural stimulation (scES) can improve bladder control and reflexive voiding efficiency in individuals with spinal cord injury. Additionally, scES has been associated with improvements in motor function and body composition, suggesting its potential to enhance multiple body functions. ^{1 2 3 4 5}

How does the treatment Epidural Stimulation + Training for Spinal Cord Injury differ from other treatments?

This treatment is unique because it uses electrical stimulation directly on the spinal cord to improve functions like bladder control and mobility, which is different from traditional therapies that may not directly target the spinal cord. It combines this stimulation with specific training exercises to enhance recovery, offering a novel approach to managing spinal cord injury effects. ^{1 3 4 6 7}

Eligibility Criteria

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

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

Your injury occurred no more than 1 year ago.

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

I rely on a machine to help me breathe.

Timeline

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

Treatment Details

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.

Participant Groups

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+

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury. [2019]

3. 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]

4. Austria pubmed.ncbi.nlm.nih.gov

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

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

Surface stimulation techniques for bladder management in the spinal dog. [2019]

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

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

7. England pubmed.ncbi.nlm.nih.gov

High-density spinal cord stimulation selectively activates lower urinary tract nerves. [2023]