Spinal Cord Stimulation for Spinal Cord Injury

(SCAP Trial)

Recruiting at 3 trial locations

Overseen By Chris E Mandigo, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Columbia University

Must not be taking: Amphetamines, Neuroleptics, Dalfampridine, Bupropion

Disqualifiers: Seizures, Stroke, Heart disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6-8 weeks

92 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Spinal cord associative plasticity (SCAP) is a combined cortical and spinal electrical stimulation technique developed to induce recovery of arm and hand function in spinal cord injury. The proposed study will advance understanding of SCAP, which is critical to its effective translation to human therapy. The purpose of the study is to: 1. Determine whether signaling through the spinal cord to the muscles can be strengthened by electrical stimulation. 2. Improve our understanding of the spinal cord and how it produces movement. 3. Determine whether spinal surgery to relieve pressure on the spinal cord can improve its function. Aim 1 is designed to advance mechanistic understanding of spinal cord associative plasticity (SCAP). Aim 2 will determine whether SCAP increases spinal cord excitability after the period of repetitive pairing. In rats, SCAP augments muscle activation for hours after just 5 minutes of paired stimuli. Whereas Aims 1 and 2 focused on the effects of paired stimulation in the context of uninjured spinal cord, Aim 3 assesses whether paired stimulation can be effective across injured cord segments. Aim 3 will incorporate the experiments from Aim 1 and 2 but in people with SCI, either traumatic or pre-operative patients with myelopathy in non-invasive experiments, or targeting myelopathic segments in intraoperative segments.

Will I have to stop taking my current medications?

The trial requires that your prescription medications remain stable for 30 days before screening, so you should not change your current medications during this time.

Is spinal cord stimulation generally safe for humans?

Spinal cord stimulation (SCS) is considered a safe and reversible treatment for certain pain conditions, with studies indicating it can be safely performed even in complex cases, such as those with epidural scar tissue. However, specific risks associated with the removal of paddle electrodes used in SCS are not well defined in the literature. ^{1 2 3 4 5}

How does the treatment for spinal cord injury using spinal cord associative plasticity (SCAP) differ from other treatments?

This treatment is unique because it uses a combination of brain and spinal cord stimulation to strengthen weak neural connections, potentially restoring voluntary movement in paralyzed muscles. Unlike other treatments, it focuses on timing-dependent synergies between the motor cortex and spinal cord to enhance muscle responses, offering a novel approach to rehabilitation. ^{4 5 6 7 8}

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

Research shows that pairing brain and spinal cord stimulation can significantly enhance muscle responses, with effects being over five times larger than brain stimulation alone. Additionally, long-term paired associative stimulation has been shown to restore voluntary movement in paralyzed muscles in some spinal cord injury patients, suggesting it can strengthen neural connections and improve motor function. ^{1 4 5 6 7}

Who Is on the Research Team?

Jason B Carmel, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with spinal cord injuries or cervical myelopathy who may undergo surgery. Able-bodied participants without neurological diseases can join too. Participants must not use certain drugs, have a history of seizures, metal implants in the head (except dental), stimulators, or severe cardiovascular issues.

Inclusion Criteria

Must be able to abstain from alcohol, smoking and caffeine consumption on the day of each experiment

Must be able to abstain from recreational drugs for the entirety of the study

I am scheduled for surgery on my neck's spine.

Exclusion Criteria

I or my family have a history of seizures.

You have had major hearing issues in the past.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo non-invasive and intraoperative paired cortical and spinal stimulation to study immediate and lasting effects of SCAP

6-8 weeks

Multiple visits for stimulation sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including muscle response measurements

4 weeks

2 visits (in-person)

Extension

Optional continuation of SCAP treatment to assess long-term effects

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Intraoperative pairing of cortical and spinal stimulation
• Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)
• Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) at or below myelopathic region
• Non-invasive pairing of cortical and spinal stimulation
• Non-invasive repeated pairing of cortical and spinal stimulation (SCAP)

Trial Overview The study tests SCAP—a technique using electrical stimulation on the brain and spine to improve arm and hand function after spinal injury. It explores if this can strengthen muscle signaling and enhance movement production by the spinal cord before or during surgery.

How Is the Trial Designed?

Group I: 5. Intraoperative participants - Lasting effects of SCAP at or below myelopathic region Experimental Treatment 2 Interventions

Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP); B) Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) at or below myelopathic region.

Group II: 4. Chronic cervical SCI participants - Lasting effects of non-invasive SCAP Experimental Treatment 1 Intervention

Participants with chronic cervical SCI will take part in the following, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP).

Group III: 3. Intraoperative participants - Lasting effects of SCAP Experimental Treatment 2 Interventions

Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery, to examine the lasting effects of repeated cortical and spinal stimulation: A) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP); B) Intraoperative repeated pairing of cortical and spinal stimulation (SCAP).

Group IV: 2. Intraoperative participants - Immediate effects of paired stimulation Experimental Treatment 2 Interventions

Participants will take part in the following if they have been scheduled for a clinically indicated cervical surgery to examine the immediate effects of combining cortical and spinal stimulation: A) Non-invasive pairing of cortical and spinal stimulation; B) Intraoperative pairing of cortical and spinal stimulation.

Group V: 1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulation Experimental Treatment 2 Interventions

Participants will take part in the following to examine the immediate effects of combining cortical and spinal stimulation: A) Non-invasive pairing of cortical and spinal stimulation; B) Non-invasive repeated pairing of cortical and spinal stimulation (SCAP).

Intraoperative pairing of cortical and spinal stimulation is already approved in United States for the following indications:

Approved in United States as Spinal Cord Associative Plasticity (SCAP) for:

• Spinal cord injury
• Amyotrophic lateral sclerosis (ALS)

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Bronx Veterans Medical Research Foundation, Inc

Collaborator

Trials

10

Recruited

750+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a proof-of-principle study involving two patients with chronic spinal cord injuries, long-term paired associative stimulation (20-24 weeks) led to significant recovery of voluntary movements, including ankle movement in one patient and grasping ability in another.

The improvements in motor function persisted for at least one month after the last stimulation session, suggesting that paired associative stimulation can strengthen neural connections in a clinically relevant way, warranting further research into its potential as a rehabilitation strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. Shulga, A., Lioumis, P., Zubareva, A., 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]

In a study involving 59 individuals undergoing cervical spine surgery, paired stimulation of the motor cortex and spinal cord significantly enhanced muscle responses, producing motor evoked potentials over five times larger than brain stimulation alone.

The effectiveness of this paired stimulation was dependent on the timing of the stimuli converging in the spinal cord, suggesting a promising approach for therapeutic neuromodulation that could benefit patients with varying degrees of spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans. McIntosh, JR., Joiner, EF., Goldberg, JL., et al.[2023]

In a study of 19 patients undergoing spinal cord stimulation (SCS) lead placement under general anesthesia, 84.2% experienced adequate stimulation coverage and significant pain relief postoperatively, demonstrating the efficacy of this approach for patients unable to undergo awake procedures.

Using compound muscle action potentials (CMAPs) for lead placement guidance proved effective, as consistent results were achieved in 17 out of 19 procedures, indicating that this method can successfully compensate for the lack of patient feedback during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiologic monitoring for placement of laminectomy leads for spinal cord stimulation under general anesthesia. Air, EL., Toczyl, GR., Mandybur, GT.[2022]

A new method for spinal paired associative stimulation (PAS) in lower limbs effectively enhances corticospinal transmission by individually estimating interstimulus intervals (ISIs) based on F-response and motor-evoked potential (MEP) latencies, achieving a significant 186% increase in MEP amplitude in healthy subjects.

This approach improves the precision of spinal PAS by ensuring accurate placement of peripheral nerve stimulation electrodes and using navigation in transcranial magnetic stimulation, making it a promising technique for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. Shulga, A., Lioumis, P., Kirveskari, E., et al.[2015]

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]

A novel surgical technique was developed for the safe placement of paddle-type spinal cord stimulation (SCS) electrodes in patients with epidural scar tissue, successfully applied in eight patients without complications.

This technique involves creating a laminotomy trough to facilitate dissection of scar tissue, ensuring safe electrode placement and adequate coverage, addressing challenges that can lead to spinal cord injury during conventional placement methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New technique for open placement of paddle-type spinal cord stimulator electrode in presence of epidural scar tissue. Pabaney, AH., Robin, AM., Schwalb, JM.[2022]

The study compared different frequencies of paired associative stimulation (PAS) applied to the spinal cord, including 0.1 Hz, 1 Hz, and 5 Hz bursts, but none were effective in consistently inducing neuroplasticity.

High variability in responses among participants indicates that spinal PAS may not be universally effective, suggesting that its therapeutic potential could depend on individual differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract. McGie, SC., Masani, K., Popovic, MR.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. [2019]

2. 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]

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

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans. [2023]

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

Electrophysiologic monitoring for placement of laminectomy leads for spinal cord stimulation under general anesthesia. [2022]

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

The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. [2015]

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

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

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

New technique for open placement of paddle-type spinal cord stimulator electrode in presence of epidural scar tissue. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract. [2021]