Neuromodulation for Spinal Cord Injury

Recruiting at 1 trial location

Overseen By Daniel C Lu, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Disqualifiers: Autonomic dysreflexia, Phrenic pacer, Depression, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 48

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called epidural stimulation to assist individuals with cervical spinal cord injuries who require a ventilator for breathing. The primary goal is to determine the treatment's safety and its potential to improve breathing function. Suitable candidates have had a spinal cord injury at the neck level for over a year and depend on a ventilator. Participants must also attend regular testing sessions over nearly two years. As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research that could enhance future treatment options.

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 prior data suggests that this method is safe for cervical spinal cord injury patients?

Research has shown that epidural stimulation is generally safe for people with spinal cord injuries. One study found that this treatment improved movement without major side effects. Another study focused on individuals with neck spinal cord injuries and confirmed the safety of epidural electrical stimulation, reporting no serious side effects. Overall, current evidence suggests that epidural stimulation poses no serious health risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Epidural stimulation is unique because it targets the spinal cord directly to improve respiratory function, which is a novel approach compared to standard treatments for spinal cord injury that often focus on rehabilitation and medication. While traditional methods may not address the underlying neural pathways, epidural stimulation uses electrical impulses to activate specific nerve circuits, potentially restoring some degree of voluntary control over muscles involved in breathing. Researchers are excited about this treatment because it offers a new way to enhance quality of life for individuals with spinal cord injuries by possibly improving critical functions that are otherwise difficult to regain.

What evidence suggests that epidural stimulation is effective for spinal cord injury?

Research has shown that epidural stimulation, which participants in this trial will receive, can help individuals with spinal cord injuries breathe better. Studies have found that electrical stimulation on the spinal cord improves breathing ability. Specifically, stimulating the upper back part of the spinal cord aids patients with complete spinal cord injuries in breathing more easily. Reviews also highlight that this method can help restore some body functions in individuals with long-term spinal cord injuries. Early findings suggest that epidural stimulation might be a promising approach for those who rely on machines to breathe due to spinal cord damage. ^{1 6 7 8 9}

Who Is on the Research Team?

Daniel C Lu, MD, PhD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with a spinal cord injury at levels C2 to C7, who rely on ventilators due to severe respiratory issues. They must be over a year post-injury, able to attend weekly sessions for up to 21 months, and have intact cognitive abilities. Excluded are those with recent lung surgery, active lung diseases, phrenic nerve paralysis or pacers, musculoskeletal issues like unhealed fractures or infections.

Inclusion Criteria

I can go to weekly tests for up to 21 months.

I can understand, follow instructions, and express my concerns.

My spinal cord injury between the C2 and C7 vertebrae is stable.

Exclusion Criteria

I had lung surgery within the last year or have a lung condition like asthma or COPD.

I do not have any broken bones, muscle issues, open wounds, or infections.

I have paralysis of the phrenic nerve.

Timeline for a Trial Participant

Screening and Baseline Testing/Training

Participants are screened for eligibility to participate in the trial and undergo baseline testing to ensure stable respiratory function before proceeding.

up to 6 months

Minimum once a month, up to twice a week

Temporary Implant

Subjects undergo temporary stimulator implant surgery to assess initial response.

1 day

24 hours overnight stay

Post-Temporary Implant Mapping/Treatment

Respiratory ability is assessed and rehabilitation regimen with the stimulator is used to re-enable respiratory function.

Variable, dependent on participant's response

Permanent Implant

Subjects undergo permanent stimulator implant surgery to further assess connectivity and response.

1 day, with up to 2 months for surgical recovery

24 hours overnight stay

Post-Permanent Implant Mapping/Treatment

Electrode pairs are optimized for respiratory function, and subjects undergo respiratory training with the stimulator.

up to 12 months

Up to twice weekly in the clinic, daily home use

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epidural stimulation

Trial Overview The study tests the safety and feasibility of implanting a cervical spinal cord stimulator in patients dependent on mechanical ventilation due to cervical SCI. It's an early-stage (phase 1) trial focusing on whether this approach can improve respiratory function in affected individuals.

How Is the Trial Designed?

Group I: Epidural Stimulation for Respiratory Function Experimental Treatment 1 Intervention

Self-controlled longitudinal safety and feasibility of stimulation and respiratory training.

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

Approved in European Union as Epidural Stimulation for:

• Chronic pain management
• Spinal cord injury rehabilitation

Approved in United States as Epidural Stimulation for:

• Chronic pain management
• Spinal cord injury rehabilitation
• Respiratory function improvement

Approved in Canada as Epidural Stimulation for:

• Chronic pain management
• Spinal cord injury rehabilitation

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The study successfully demonstrated the feasibility of implanting surgical paddle electrodes in the cervical and thoracic spine using a minimally invasive endoscopic technique, with all procedures completed without complications in four cadavers.

No dura rupture occurred during the surgeries, and the implantation was efficient, with most operations taking less than one hour, indicating a promising alternative to traditional open surgery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantation of Surgical Paddle Electrodes Using Percutaneous Biportal-Endoscopic Technique for Spinal Cord Stimulation: An Anatomical Feasibility Study in Human Cadavers. Li, C., Jiang, Y., Liu, T., 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]

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]

Epidural spinal cord stimulation (SCS) is an effective treatment for neuropathic pain conditions like complex regional pain syndrome and chronic radiculopathy, particularly after conservative therapies have failed.

Successful use of epidural SCS requires careful patient selection and should be part of a comprehensive treatment plan, implemented only in specialized centers to manage potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines]. Tronnier, V., Baron, R., Birklein, F., et al.[2021]

A case study of a 24-year-old woman with an implanted spinal cord stimulator (SCS) for chronic pain showed that she was able to intermittently reactivate the device during her pregnancy without any reported complications, suggesting that some women may manage SCS use during pregnancy cautiously.

Despite the lack of conclusive evidence regarding the safety of SCS during pregnancy, the case indicates that women who have kept their SCS activated have delivered healthy babies, highlighting the need for more research to better understand the risks and benefits of SCS use in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Cord Stimulation for Complex Regional Pain Syndrome: A Case Study of a Pregnant Female. Ahmed, S., Lindsay, JM., Snyder, DI.[2022]

In a study of 8326 patients who underwent spinal cord stimulation (SCS) implantation, the overall incidence of spinal cord injury (SCI) was found to be low at 2.13%, indicating that SCS is a generally safe procedure.

There was no significant difference in the rates of SCI or spinal hematoma between patients receiving percutaneous (2.35%) and paddle (1.71%) electrode implantation, suggesting similar safety profiles for both methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. Petraglia, FW., Farber, SH., Gramer, R., et al.[2022]

In a study of 35 patients who underwent spinal cord stimulator (SCS) paddle removal, the procedure was performed safely with a low complication rate, reporting only two cases of superficial infections that were easily treated with antibiotics.

The use of neuromonitoring and fluoroscopy during the procedure contributed to the minimal risk, demonstrating that SCS paddle removal can be effectively managed with careful surgical techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques for Safe Removal of Spinal Cord Stimulation Paddle Leads. Topp, G., Harland, T., Spurgas, M., et al.[2022]

Spinal cord stimulation (SCS) is generally considered a safe procedure, but this report highlights four cases of neurological complications, including paraparesis, following SCS implantation, indicating that while rare, such injuries can occur.

Among the four patients, one experienced complete paraplegia, two had incomplete paraparesis, and one fully recovered, suggesting that outcomes can vary significantly and further research is needed to understand the true incidence of neurological injuries related to SCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A report of paraparesis following spinal cord stimulator trial, implantation and revision. Smith, CC., Lin, JL., Shokat, M., et al.[2011]

In a study of 68 patients who had spinal cord stimulation paddle electrodes removed, the most common reason for removal was loss of coverage or effect (75%), indicating that while SCS is effective, it may not always provide lasting relief.

Postoperative complications occurred in 11.75% of patients, with two major complications requiring reoperation, highlighting that while SCS removal is generally safe, it does carry some risks that patients should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. Maldonado-Naranjo, AL., Frizon, LA., Sabharwal, NC., et al.[2022]

Spinal cord stimulation (SCS) is an effective treatment for intractable neuropathic pain, showing better outcomes compared to conventional medical management and reoperation, particularly in patients with failed back surgery syndrome.

Recent studies indicate that paresthesia-free SCS methods, such as burst, high-density, and 10-kHz frequency stimulation, are generally superior to traditional tonic SCS, and patients show a strong preference for these newer techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tonic, Burst, High-Density, and 10-kHz High-Frequency Spinal Cord Stimulation: Efficiency and Patients' Preferences in a Failed Back Surgery Syndrome Predominant Population. Review of Literature. Peeters, JB., Raftopoulos, C.[2021]

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]

Spinal cord stimulation (SCS) is an effective surgical option for patients suffering from chronic neuropathic pain that does not respond to traditional medical treatments.

The SCS system involves implanting leads in the epidural space, which are connected to a pulse generator, showcasing advancements in technology and surgical techniques for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History and Future of Spinal Cord Stimulation. Ali, R., Schwalb, JM.[2023]

In a study of 20 comatose patients, cervical spinal cord stimulation (SCS) significantly increased cerebral blood perfusion and levels of dopamine and norepinephrine in cerebrospinal fluid after six months, indicating potential benefits for brain function.

SCS also reduced oxidative stress by decreasing superoxide free radicals in the blood, suggesting it may help improve overall brain health in comatose patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of electrical cervical spinal cord stimulation on cerebral blood perfusion, cerebrospinal fluid catecholamine levels, and oxidative stress in comatose patients. Liu, JT., Tan, WC., Liao, WJ.[2019]

Spinal cord stimulation (SCS) shows potential effectiveness in treating chronic pain conditions like Complex Regional Pain Syndrome Type I and Failed Back Surgery Syndrome, based on two trials involving 81 patients, although the evidence is limited and more research is needed.

The studies reviewed had varying quality, with one high-quality trial and one low-quality trial, indicating a need for better-designed studies to accurately assess the efficacy and safety of SCS in chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic pain. Mailis-Gagnon, A., Furlan, AD., Sandoval, JA., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10889415/

Epidural Spinal Cord Stimulation for Spinal Cord Injury in ... This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety.

2. reporter.nih.gov reporter.nih.gov/project-details/11045781

Epidural spinal cord stimulation and respiratory motor function ... Our previous findings demonstrate that respiratory function in patients with chronic spinal cord injury can be improved by using our original inspiratory- ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1569904822000441

Epidural electrical spinal cord stimulation of the thoracic ... Epidural electrical spinal cord stimulation of the thoracic segments (T2-T5) facilitates respiratory function in patients with complete spinal cord injury.

4. e-neurospine.org e-neurospine.org/journal/view.php?doi=10.14245/ns.2244652.326

A Review of Functional Restoration From Spinal Cord ... This review aims to assess the efficacy of spinal cord stimulation, both epidural (eSCS) and transcutaneous (tSCS), on the return of function in individuals ...

5. journals.physiology.org journals.physiology.org/doi/abs/10.1152/jn.00625.2020

Electrical epidural stimulation of the cervical spinal cord Spinal synaptic enhancement with acute intermittent hypoxia improves respiratory function after chronic cervical spinal cord injury. J Neurosci 25: 2925 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07105878

Epidural Electrical Stimulation in Spinal Cord Injury The goal of this clinical trial is to evaluate the safety and effectiveness of Epidural Electrical Stimulation (EES) in motor and sensory function ...

7. nature.com nature.com/articles/s41591-024-02940-9

Non-invasive spinal cord electrical stimulation for arm and ... These results demonstrate the safety and efficacy of ARC EX Therapy to improve hand and arm functions in people living with cervical SCI.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8374568/

Epidural electrical stimulation for spinal cord injury - PMC In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function.

9. spj.science.org spj.science.org/doi/10.34133/cbsystems.0314

Epidural Electrical Stimulation for Functional Recovery in ... This study confirms the promising therapeutic effects of EES in SCI. EES combined with PT provides a potential approach for functional recovery in patients ...