Neuromodulation for Spinal Cord Injury

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Daniel C Lu, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of California, Los Angeles

Disqualifiers: Autonomic dysreflexia, Phrenic pacer, Depression, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests a small device placed near the neck's spinal cord to help people with severe spinal injuries who need ventilators. It aims to see if electrical signals from the device can improve their breathing. The study focuses on adults aged 18-75 with injuries between C2 and C7 vertebrae. The goal is to reduce the need for ventilators in these 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Epidural Stimulation for spinal cord injury?

Research shows that epidural spinal cord stimulation (SCS) can improve physical function after spinal cord injury and has been used successfully for chronic pain and motor disturbances. In some cases, it has improved mobility and reduced spasticity (muscle stiffness) in patients with conditions like multiple sclerosis and myelopathy. ^{1 2 3 4 5}

Is spinal cord stimulation generally safe for humans?

Spinal cord stimulation (SCS) is generally considered safe and has been used for over 40 years to treat chronic pain conditions. While rare, some complications like spinal cord injury have been reported, but the most common issues are equipment-related without causing neurological harm. ^{6 7 8 9 10}

How is epidural stimulation different from other treatments for spinal cord injury?

Epidural stimulation is unique because it involves placing electrodes in the spinal epidural space to alter nerve activity, which can help improve movement after a spinal cord injury. Unlike other treatments, it can be combined with brain stimulation to enhance its effects, and it is part of a growing field of neuromodulation therapies that are being explored for their potential to induce long-term changes in the nervous system. ^{3 11 12 13 14}

Research Team

Daniel C Lu, MD, PhD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Epidural stimulation (Neuromodulation)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Thomas Rando

University of California, Los Angeles

Chief Medical Officer since 2023

MD from UCLA

Amir Naiberg

University of California, Los Angeles

Chief Executive Officer since 2024

JD from UCLA

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Jordan Gladman

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Medical Officer

MD from Harvard Medical School

Walter J. Koroshetz

National Institute of Neurological Disorders and Stroke (NINDS)

Chief Executive Officer since 2007

MD from the University of Chicago

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

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 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]

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]

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]

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 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 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]

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]

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]

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. Germany pubmed.ncbi.nlm.nih.gov

[Epidural spinal cord stimulation for therapy of chronic pain. Summary of the S3 guidelines]. [2021]

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

History and Future of Spinal Cord Stimulation. [2023]

4. Austria 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. [2019]

5. Austria pubmed.ncbi.nlm.nih.gov

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

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

Spinal Cord Stimulation for Complex Regional Pain Syndrome: A Case Study of a Pregnant Female. [2022]

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

A report of paraparesis following spinal cord stimulator trial, implantation and revision. [2011]

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

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation. [2022]

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

Rate of Complications Following Spinal Cord Stimulation Paddle Electrode Removal. [2022]

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

Techniques for Safe Removal of Spinal Cord Stimulation Paddle Leads. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Combined neuromodulatory approaches in the central nervous system for treatment of spinal cord injury. [2023]

12. United States 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. [2023]

13. United States 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. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic pain. [2018]