Health TrialsbyHealthPanel

Spinal Cord Associative Plasticity Study

ConditionsCervical Spinal Cord InjuryTetraplegia/TetraparesisCervical Myelopathy
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorColumbia University

About 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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

No known central or peripheral neurological disease or injury.

Disqualifiers

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;

Trial design

Design model

Crossover

Treatments tested in this trial

  • Non-invasive pairing of cortical and spinal stimulation

    Procedure/Surgery

    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

    Procedure/Surgery

    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)

    Procedure/Surgery

    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)

    Procedure/Surgery

    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

    Procedure/Surgery

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

Treatment groups

92 Participants
are divided into 5 treatment groups
Group A: 1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulationExperimental treatment 2 interventions
Group B: 2. Intraoperative participants - Immediate effects of paired stimulationExperimental treatment 2 interventions
Group C: 3. Intraoperative participants - Lasting effects of SCAPExperimental treatment 2 interventions
Group D: 4. Chronic cervical SCI participants - Lasting effects of non-invasive SCAPExperimental treatment 1 intervention
Group E: 5. Intraoperative participants - Lasting effects of SCAP at or below myelopathic regionExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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
2

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Columbia University

Lead sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Weill Medical College of Cornell University

Collaborator

Bronx Veterans Medical Research Foundation, Inc

Collaborator

Source ClinicalTrials.gov
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