An Early Phase 1 interventional study of Non-invasive pairing of cortical and spinal stimulation and Intraoperative pairing of cortical and spinal stimulation in Cervical Spinal Cord Injury, Tetraplegia/Tetraparesis and Cervical Myelopathy, sponsored by Columbia University. Recruiting at 3 sites in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-18.
Sponsored by Columbia University · Early Phase 1, Interventional, and Basic science
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:
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.
For people with cervical spinal cord injury (SCI), regaining hand function is their highest priority. Currently there are no effective treatments for people living with paralysis or profound weakness after SCI. The goal of this project is to translate a promising therapy for improving arm and hand function after partial spinal cord injury to humans. The approach promotes repair of residual brain to spinal cord connections using combined motor cortex and spinal cord stimulation.
The direct brain to spinal cord connection is critical for skilled hand movement in health, and for the loss of movement after injury. After spinal cord injury, many nerve connections for movement are preserved. These connections can be strengthened by electrical stimulation.
The investigator has previously demonstrated that pairing brain and spinal cord stimulation strengthens spinal connections in rats. But it is unknown whether this is also applicable in humans. This study is designed to test this in people undergoing spine surgery for pain or decreased movement as well as non-invasively in people with traumatic spinal cord injury. There are three main goals of this project. First, the investigator will stimulate brain and spinal cord (intra-operatively and non-invasively) to try to study the influence of the timing of pairing brain and spinal cord stimulation. Second, the investigator will study how repeating the optimal timing (spinal cord associative plasticity; SCAP) will influence muscle responses over a longer period of time when relatively uninjured parts of the spinal cord are targeted. Finally, the investigator will study how the influence of this protocol changes when injured parts of the cord are targeted. Stimulation of brain and spinal cord intra-operatively will be performed with the same devices that maintain safety during the surgery, while non-invasive stimulation will be performed with non-significant risk devices.
Participants: Uninjured volunteers, individuals with chronic (> 1 year) cervical SCI, and individuals with cervical myelopathy or radiculopathy requiring clinically indicated decompressive surgery will be recruited. SCI and myelopathy participants will have partially retained motor function in the hand, scoring 1-4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand. Participants will also require detectable F-wave responses of the left or right abductor pollicis brevis (APB) to median nerve stimulation and/or first dorsal interosseous muscle (FDI) to ulnar nerve stimulation.
189 studies on the registry are indexed under Quadriplegia; 72 are open to participants now.
This study's planned enrollment of 92 is above the median of 13 across 162 interventional studies indexed under Quadriplegia.
Browse Quadriplegia studies →Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.
Of its 172 completed or terminated interventional studies of FDA-regulated products, 142 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
NON-INVASIVE
Inclusion Criteria:
(All participants)
(Able-bodied participants)
(SCI participants - including patients scheduled for intraoperative procedures)
Exclusion criteria:
(All participants)
INTRA-OPERATIVE
Inclusion Criteria:
Exclusion criteria:
(For experiments involving cortical 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).
Procedure: Non-invasive pairing of cortical and spinal stimulation · Procedure: Non-invasive repeated pairing of cortical and spinal stimulation (SCAP)
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.
Procedure: Non-invasive pairing of cortical and spinal stimulation · Procedure: Intraoperative pairing of cortical and spinal stimulation
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).
Procedure: Non-invasive repeated pairing of cortical and spinal stimulation (SCAP) · Procedure: Intraoperative repeated pairing of cortical and spinal stimulation (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).
Procedure: Non-invasive repeated pairing of cortical and spinal stimulation (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) at or below myelopathic region.
Procedure: Non-invasive repeated pairing of cortical and spinal stimulation (SCAP) · Procedure: Intraoperative repeated pairing of cortical and spinal stimulation (SCAP) at or below myelopathic region
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.
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.
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: 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.
As per the intervention 'Intraoperative repeated pairing of cortical and spinal stimulation (SCAP)' targeted at or below myelopathic region.
Size of hand muscle response to brain stimulation during combined brain and spinal stimulation
Size of hand muscle response will be measured in response to brain and spinal cord stimulation timed to converge in the spinal cord. This value will be normalized to the muscle response for brain only stimulation. This applies to Arms 1-2.
Time frame: Immediate
Size of hand muscle response to brain stimulation after SCAP
Size of hand muscle response will be measured in response to brain and spinal cord stimulation timed to converge in the spinal cord. This value will be normalized to the equivalent measure taken before the SCAP protocol. This applies to Arms 3-5.
Time frame: Immediately after SCAP
Size of hand muscle response to spinal cord stimulation
Size of hand muscle response will be measured in response to brain and spinal cord stimulation timed to converge in the spinal cord. This value will be normalized to the equivalent measure taken before the SCAP protocol.
Time frame: Immediately after SCAP
Duration of effect of SCAP on subsequent responses to brain or spinal cord stimulation
Time taken for the size of hand muscle response to fall to 50% of its maximal post-SCAP level.
Time frame: 1 hour after SCAP
Pinch force
Pinch opposition strength between the tips of the thumb and third finger (a task highly dependent on cortical transmission to C8-T1 spinal circuitry will be measured using a handheld dynamometer. Force and root mean square (RMS) of electromyographic activity will be recorded. Maximal pinch dynamometry will be compared to baseline measurement.
Time frame: Immediately after SCAP
Amplitudes of H-reflex ratio
H-reflex amplitudes (Hmax/Mmax), a biomarker for spasticity triggered with 1.0 ms pulses over the median nerve at the elbow.
Time frame: Immediately after SCAP
Threshold for triggering muscle response from brain stimulation
The threshold for transcutaneous cortical electrical stimulation will be measured by increasing the voltage from 50V in 50V steps, until a MEP is detected.
Time frame: Immediately after SCAP
Threshold for triggering muscle response from spinal cord stimulation
The threshold for spinal cord stimulation will be measured by increasing the stimulation amplitude from 1mA in 1mA steps, until an evoked potential is observable in the target muscle, or our safety limit is reached. In cases where clear evoked responses cannot be generated within stimulation amplitude safety limits, 3 pulse stimuli will be used, or investigator will modify target muscle for the remainder of the experiment. Study will target APB, but more responsive muscles may be substituted.
Time frame: Immediately after SCAP
Size of hand muscle response to spinal cord stimulation (lasting)
Size of hand muscle response will be measured in response to brain and spinal cord stimulation timed to converge in the spinal cord. This value will be normalized to the equivalent measure taken before the SCAP protocol.
Time frame: 30 minutes after SCAP
Pinch force (lasting)
Pinch opposition strength between the tips of the thumb and third finger (a task highly dependent on cortical transmission to C8-T1 spinal circuitry will be measured using a handheld dynamometer. Force and root mean square (RMS) of electromyographic activity will be recorded. Maximal pinch dynamometry will be compared to baseline measurement.
Time frame: 30 minutes after SCAP
Amplitudes of H-reflex ratio (lasting)
H-reflex amplitudes (Hmax/Mmax), a biomarker for spasticity triggered with 1.0 ms pulses over the median nerve at the elbow.
Time frame: 30 minutes after SCAP
Threshold for triggering muscle response from brain stimulation (lasting)
The threshold for spinal cord stimulation will be measured by increasing the stimulation amplitude from 1mA in 1mA steps, until an evoked potential is observable in the target muscle, or our safety limit is reached. In cases where clear evoked responses cannot be generated within stimulation amplitude safety limits, 3 pulse stimuli will be used, or investigator will modify target muscle for the remainder of the experiment. Study will target APB, but more responsive muscles may be substituted.
Time frame: 30 minutes after SCAP
Plan to share: Yes — Deidentified, individual-level data will be deposited to appropriate public repositories, such as Open Data Commons for Spinal Cord Injury (https://scicrunch.org/odc-sci), Figshare, or others. This will allow more powerful meta-analysis of disparate smaller studies, a need which is even more urgent in neurorehabilitation than in other fields that are more amenable to large drug studies.
Supporting information: Study protocol, Sap
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Columbia University