Clinical trial NCT05163639: Spinal Cord Associative Plasticity Study
Official title: Spinal Cord Associative Plasticity Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Cervical Spinal Cord Injury
Tetraplegia/Tetraparesis
Cervical Myelopathy
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
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Weill Medical College of Cornell University
name: Bronx Veterans Medical Research Foundation, Inc
First posted: 2021-12-20
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants with chronic SCI, participants with spondylotic radiculopathy or myelopathy scheduled to undergo elective cervical decompression surgery, and volunteers without neural injury will be prospectively enrolled in this interventional experimental study.
Primary purpose: BASIC_SCIENCE

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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Size of hand muscle response to brain stimulation during combined brain and spinal stimulation
timeFrame: Immediate
measure: Size of hand muscle response to brain stimulation after SCAP
timeFrame: Immediately after SCAP
Secondary outcomes:
measure: Size of hand muscle response to spinal cord stimulation
timeFrame: Immediately after SCAP
measure: Duration of effect of SCAP on subsequent responses to brain or spinal cord stimulation
timeFrame: 1 hour after SCAP
measure: Pinch force
timeFrame: Immediately after SCAP
measure: Amplitudes of H-reflex ratio
timeFrame: Immediately after SCAP
measure: Threshold for triggering muscle response from brain stimulation
timeFrame: Immediately after SCAP
measure: Threshold for triggering muscle response from spinal cord stimulation
timeFrame: Immediately after SCAP
measure: Size of hand muscle response to spinal cord stimulation (lasting)
timeFrame: 30 minutes after SCAP
measure: Pinch force (lasting)
timeFrame: 30 minutes after SCAP
measure: Amplitudes of H-reflex ratio (lasting)
timeFrame: 30 minutes after SCAP
measure: Threshold for triggering muscle response from brain stimulation (lasting)
timeFrame: 30 minutes after SCAP
Other outcomes:
Locations:
city: New York
country: United States
facility: Bronx Veterans Medical Research Foundation, Inc
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Columbia University
name: Jason B Carmel, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: