Recruiting
Early Phase 1

Spinal Cord Plasticity

Sponsor:

Columbia University

Code:

NCT05163639

Conditions

Cervical Spinal Cord Injury

Tetraplegia/Tetraparesis

Cervical Myelopathy

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Non-invasive pairing of cortical and spinal stimulation

Intraoperative pairing of cortical and spinal stimulation

Non-invasive repeated pairing of cortical and spinal stimulation (SCAP)

Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)

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

Study Details

Brief summary:

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.

Conditions

Cervical Spinal Cord Injury

Tetraplegia/Tetraparesis

Cervical Myelopathy

Study ID

NCT05163639

Start date

Sep 10, 2021

Status verified date

Jun, 2026

Completion date

Dec 30, 2027

Anticipated

Primary completion date

Dec 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

NON-INVASIVE

Inclusion Criteria:

(All participants)

  • Age between 18-80 years.
  • Must have stable prescription medication for 30 days prior to screening
  • Must be able to: abstain from alcohol, smoking and caffeine consumption on the day of each experiment; abstain from recreational drugs for the entirety of the study; commit to study requirements (i.e., 7 visits); provide informed consent.

(Able-bodied participants)

  • No known central or peripheral neurological disease or injury.

(SCI participants - including patients scheduled for intraoperative procedures)

  • Score of 1-4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand.

Exclusion criteria:

(All participants)

  • Personal or extensive family history of seizures;
  • Ventilator dependence or patent tracheostomy site;
  • Use of medications that significantly lower seizure threshold, such as amphetamines, neuroleptics, dalfampridine, and bupropion;
  • History of stroke, brain tumor, brain abscess, or multiple sclerosis;
  • History of moderate or severe head trauma (loss of consciousness for greater than one hour or evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging);
  • History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except for inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain or spine stimulation;
  • Significant coronary artery or cardiac conduction disease; recent history of myocardial infarction and heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV;
  • Recent history (within past 6 months) of recurrent autonomic dysreflexia, defined as a syndrome of sudden rise in systolic pressure greater than 20 mm Hg or diastolic pressure greater than 10 mm Hg, without rise in heart rate, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (this will be closely monitored during all screening and testing procedures);
  • History of significant hearing problems;
  • History of bipolar disorder;
  • History of suicide attempt;
  • Active psychosis;
  • Recent history (>1 year) of chemical substance dependency or significant psychosocial disturbance;
  • Heavy alcohol consumption (greater than equivalent of 5oz of liquor) within previous 48 hours;
  • Open skin lesions over the face, neck, shoulders, or arms;
  • Pregnancy; and
  • Unsuitable for study participation as determined by study physician.

INTRA-OPERATIVE

Inclusion Criteria:

  • Clinical indication for cervical spine surgery.

Exclusion criteria:

(For experiments involving cortical stimulation)

  • Epilepsy;
  • A history of skull surgery with metal implants;
  • Cochlear implants;
  • Patients with aneurysm stents in neck or brain blood vessels;
  • Evidence of skull shrapnel; (For experiments involving spinal cord stimulation)
  • Stimulation devices in the neck or chest (e.g., vagal nerve stimulation, cardiac patients with pacemakers)

Study Design

Enrollment

92 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: 1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulation

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).

experimental: 2. Intraoperative participants - Immediate effects of paired stimulation

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.

experimental: 3. Intraoperative participants - Lasting effects of SCAP

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).

experimental: 4. Chronic cervical SCI participants - Lasting effects of non-invasive SCAP

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).

experimental: 5. Intraoperative participants - Lasting effects of SCAP at or below myelopathic region

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.

Interventions

Non-invasive pairing of cortical and spinal stimulation

Transcranial magnetic stimulation (TMS) threshold, Transcutaneous spinal cord stimulation (TSCS) threshold, and peripheral and central motor conduction times will be determined. In the active intervention, two TMS pulse intensities will be tested: 90% and 120% of motor threshold. Two conditioning TSCS pulse intensities will be tested: 50% and 90% of response threshold. Single TSCS pulses will be delivered timed to arrive in the cervical spinal cord at a range of intervals from 30ms before to 30ms after the TMS pulse. The control conditions will include TMS only TSCS only and non-convergent pairing latency pairing stimulation.

Intraoperative pairing of cortical and spinal stimulation

The surgeon will position spinal cord electrodes on the epidural surface one level rostral (typically C4/C5) to the site of myelopathy. Spinal and cortical thresholds will be determined. Investigator will then test the immediate effects of paired stimulation by stimulating the cortex at 120% of threshold and the spinal cord at 90% of threshold at various latencies relative to the time of synchronous convergence. The control intervention will include cortical only (120%) spinal only (90%) and non-convergent latency pairing stimulation.

Non-invasive repeated pairing of cortical and spinal stimulation (SCAP)

Thresholds will be determined as above. Immediately prior to repetitive pairing, a set of 12 TMS pulses will be delivered at 120% threshold to measure the baseline cortical MEP. Likewise, a set of 12 TSCS pulses will be delivered at 120% of threshold to establish the baseline spinal MEP. For each session, baseline maximal pinch dynamometry will be determined. Immediately after the SCAP protocol is completed, response to TMS, TSCS, and maximal pinch dynamometry will be measured again every 10 minutes over the subsequent hour. The control conditions will include TMS only TSCS only and non-convergent pairing latency pairing stimulation.

Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)

Intraoperative: Spinal and cortical thresholds will be determined. Immediately prior to repetitive pairing, a set of 12 baseline cortical pulses and 12 baseline spinal pulses will be delivered at 120% threshold. SCAP protocol will be applied, both of which have been successful at inducing lasting effects in the rat. After pairing, cortical stimulation at 120% of threshold and spinal cord stimulation at 120% threshold will be repeated every 10 minutes for the duration of surgery. In a subset of patients repeated pairing will be conducted with a latency that investigator does not expect will induce SCAP, or with electrodes placed over the ventral epidural surface. The control intervention will include repeated pairing at a non-convergent latency, as well as pairing of cortical stimulation with ventral epidural stimulation.

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

As per the intervention 'Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)' targeted at or below myelopathic region.

Primary outcome measure

  • Size of hand muscle response to brain stimulation during combined brain and spinal stimulation [ Time Frame: Immediate ]
  • Size of hand muscle response to brain stimulation after SCAP [ Time Frame: Immediately after SCAP ]

Central Contacts and Locations

Central contacts

Jason B Carmel, M.D., Ph.D.

917-301-1882jbc28@cumc.columbia.edu

Noam Y Harel, M.D., Ph.D.

212-241-7317noam.harel@mssm.edu

Locations

Bronx Veterans Medical Research Foundation, Inc

Recruiting

New York, New York, United States, 10029

Contacts

Noam Y Harel, M.D., Ph.D.

718-584-9000Noam.harel@va.gov

Principal Investigator:

Noam Y Harel, M.D., Ph.D.

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

Jason B Carmel, MD, PhD

212-305-6616jbc28@cumc.columbia.edu

Principal Investigator:

Jason B Carmel, M.D.

Weill Cornell Medicine

Recruiting

New York, New York, United States, 10065

Contacts

Michael S Virk, M.D., Ph.D.

(503) 494-4723miv2010@med.cornell.edu

Principal Investigator:

Michael S Virk, M.D., Ph.D.

More Information

Sponsor

Columbia University

Last update posted

Jun 18, 2026

Last verified

Jun, 2026

Keywords

  • spinal cord injury
  • paired brain and spinal cord stimulation
  • convergent stimulation
  • spinal cord associative plasticity
  • transcutaneous spinal cord stimulation
  • intraoperative monitoring
  • upper-limb muscle activation
  • motor cortex
  • cervical spinal cord

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Columbia University on 2026-06-18.