Spine and Brain Stimulation for Spinal Cord Injury

Recruiting at 1 trial location

Overseen By Emelly Carrasco

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jason Carmel

Must not be taking: Seizure threshold-lowering

Disqualifiers: Seizures, Bipolar, Heart disease, others

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

Compensation: Varies

Number of Visits: 29

Duration: 4 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

Stimulation of the spinal cord and brain represents a new experimental therapy that may have potential to restore movement after spinal cord injury. While some scientists have begun to study the effect of electrical stimulation on patient's ability to walk and move their legs after lower spinal cord injury, the use of stimulation of the upper (cervical) spine to restore arm and hand function after cervical spinal cord injury remains less well explored. The investigators are doing this research study to improve understanding of whether cervical spinal cord stimulation and brain stimulation can be used to improve arm and hand function. To do this, the investigators will combine spine stimulation (in the form of electrical stimulation from electrical stimulation wires temporarily implanted next to the cervical spinal cord) and brain stimulation (in the form of transcranial magnetic stimulation). The investigators will perform a series of experiments over 29 days to study whether these forms of stimulation can be applied and combined to provide improvement in arm and hand function.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on medications that lower the seizure threshold, you may need to stop those to participate.

What data supports the effectiveness of the treatment Epidural Spinal Cord Stimulation, Paired Spine and Brain Stimulation for spinal cord injury?

Research shows that epidural spinal cord stimulation can help improve motor function in people with spinal cord injuries by activating nerve circuits that control movement. This treatment, especially when combined with specific training exercises, can help paralyzed individuals regain some ability to stand, step, and move their legs. ^{1 2 3 4 5}

Is spinal cord stimulation generally safe for humans?

Spinal cord stimulation (SCS) has been used for over 40 years and is considered a safe option for treating chronic pain, with well-defined complication rates. Studies have shown it to be effective and safe in various populations, including veterans, although specific risks like spinal cord injury are not fully quantified. ^{6 7 8 9 10}

How does the treatment 'Spine and Brain Stimulation for Spinal Cord Injury' differ from other treatments for this condition?

This treatment is unique because it combines epidural spinal cord stimulation with brain stimulation, timed to enhance motor responses by converging signals in the spinal cord. This approach aims to improve motor function by activating specific neural circuits, which is different from traditional methods that may not target these precise pathways. ^{1 2 5 11 12}

Research Team

Jason B. Carmel, MD, PhD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for English-speaking adults over 18 with incomplete traumatic spinal cord injury between C4 to T1, who have some motor power in at least one upper extremity muscle group. Participants must be able to understand and follow instructions and consent to the study. Exclusions include a history of suicide attempts, ongoing ventilator use, certain metal implants or brain stimulators, severe psychiatric disorders, substance abuse affecting seizure risk, pregnancy plans during the study period, specific medical conditions or treatments that could interfere with the trial.

Inclusion Criteria

English speaking

International Standards for Neurological Classification of Spinal Cord Injury Upper Extremity Motor Score (ISNCSCI-UEMS) ≤ 40/50

Ability and willingness to provide informed consent

Exclusion Criteria

Any history of suicide attempt

Any ongoing ventilator use (continuous or intermittent)

Intracranial aneurysm clips

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo temporary placement of cervical epidural spinal cord stimulation (SCS) electrodes and participate in a series of experiments over 29 days to study the effects of SCS and brain stimulation on arm and hand function.

4 weeks

Daily visits for 29 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of adverse events and tolerability.

26 weeks

Treatment Details

Interventions

• Epidural Spinal Cord Stimulation
• Paired Spine and Brain Stimulation

Trial Overview The trial tests whether combining cervical spinal cord stimulation (electrical wires implanted near the spine) with transcranial magnetic brain stimulation can improve arm and hand function after an upper spinal cord injury. Over 29 days, experiments will assess if this dual approach offers functional benefits.

Participant Groups

Group I: Epidural Spinal Cord Stimulation Experimental Treatment 1 Intervention

Participants will undergo temporary placement of cervical epidural spinal cord stimulation (SCS) electrodes. They will undergo 2 visits of stimulation optimization based on mapping of motor responses to SCS and clinical assessments at a range of SCS parameters. Once a stimulation plan has been established, subjects will undergo baseline assessments with and without SCS over 2 visits. Subjects will then undergo 15 days of continuous SCS in conjunction with structured rehabilitation with occupational therapy. On each day of therapeutic stimulation, subjects will receive two sessions of SCS plus structured rehabilitation (for up to 1.5 hours per session). Subjects will undergo a clinical assessment with and without stimulation at the midpoint of the therapeutic stimulation period. After this therapeutic stimulation period, subjects will undergo 2 days of repeat assessments.

Who Is Running the Clinical Trial?

Jason Carmel

Lead Sponsor

Trials

1

Recruited

20+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Spinal cord stimulation (SCS) is evolving from a treatment for intractable pain to a potential method for restoring function after spinal cord injuries, driven by advances in understanding spinal cord lesions and compensatory mechanisms.

New SCS strategies, like spatiotemporal neuromodulation, show promise but require intensive rehabilitation techniques to be effective, highlighting the need for well-designed clinical trials to evaluate safety and efficacy in real-world applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks. Pradat, PF., Hayon, D., Blancho, S., et al.[2023]

Epidural spinal cord stimulation can activate spared neural circuitry below severe spinal cord injuries, enabling paralyzed individuals to achieve motor outputs like standing and stepping during assisted treadmill exercises.

This stimulation not only generates immediate motor responses but also supports rehabilitation by promoting long-term neural plasticity, potentially leading to lasting improvements in motor function for patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. Minassian, K., Hofstoetter, US.[2020]

Epidural spinal cord stimulation can effectively elicit spinal motor evoked potentials (sMEPs) in forelimb muscles of rats after spinal cord injury, with the strength of these responses varying based on electrode placement and stimulation intensity.

sMEPs can serve as reliable biomarkers to optimize stimulation parameters for improving forelimb motor function, suggesting a more efficient method for determining effective treatment configurations compared to traditional empirical testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats. Alam, M., Garcia-Alias, G., Shah, PK., et al.[2018]

In a study involving 122 participants with chronic low back and/or leg pain, multiphase spinal cord stimulation (SCS) significantly reduced pain levels, with mean reductions of -4.3 and -4.7 on the numerical rating scale for two different multiphase therapies.

The multiphase SCS therapies were found to be safe, with only one non-serious device-related adverse event reported and no infections, suggesting a favorable safety profile for this new stimulation paradigm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. Kapural, L., Patterson, DG., Li, S., et al.[2023]

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]

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 402 patients with chronic pain who received spinal cord stimulation (SCS) devices, 55% of those with lower limb pain and 67% with upper limb pain reported a significant reduction in pain (≥50% reduction) after 2 years, indicating the long-term effectiveness of SCS.

The majority of patients (91%) were satisfied with their treatment, and 93% would choose to undergo the procedure again, while also showing a significant decrease in the need for pain medications, highlighting both the efficacy and safety of SCS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic refractory pain: Long-term effectiveness and safety data from a multicentre registry. Brinzeu, A., Cuny, E., Fontaine, D., et al.[2019]

Pairing motor cortex stimulation with spinal cord epidural stimulation significantly enhances motor responses, particularly when the timing of the stimuli is optimized, leading to more than double the motor evoked potentials (MEPs).

Repeated stimulation of both areas not only produced immediate effects but also resulted in lasting increases in spinal excitability and MEPs, suggesting a potential therapeutic approach for improving sensorimotor function after central nervous system injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses. Mishra, AM., Pal, A., Gupta, D., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in Spinal Cord Neuromodulation: The Integration of Neuroengineering, Computational Approaches, and Innovative Conceptual Frameworks. [2023]

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

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. [2020]

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

Spinal Cord Epidural Stimulation for Lower Limb Motor Function Recovery in Individuals with Motor Complete Spinal Cord Injury. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of optimal electrode configurations for epidural spinal cord stimulation in cervical spinal cord injured rats. [2018]

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

Multiphase Spinal Cord Stimulation in Participants With Chronic Back or Leg Pain: Results of the BENEFIT-02 Randomized Clinical Trial. [2023]

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

Review of Efficacy and Safety of Spinal Cord Stimulation in Veterans. [2023]

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

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

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Spinal cord stimulation for chronic refractory pain: Long-term effectiveness and safety data from a multicentre registry. [2019]

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

Paired motor cortex and cervical epidural electrical stimulation timed to converge in the spinal cord promotes lasting increases in motor responses. [2018]

12. Ireland pubmed.ncbi.nlm.nih.gov

Cortical potentials evoked by epidural stimulation of the cervical and thoracic spinal cord in man. [2019]