NCT05163639

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. 1.Determine whether signaling through the spinal cord to the muscles can be strengthened by electrical stimulation.
  2. 2.Improve our understanding of the spinal cord and how it produces movement.
  3. 3.Determine whether spinal surgery to relieve pressure on the spinal cord can improve its function.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
92

participants targeted

Target at P75+ for early_phase_1

Timeline
1mo left

Started Sep 2021

Longer than P75 for early_phase_1

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress97%
Sep 2021Jun 2026

Study Start

First participant enrolled

September 10, 2021

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 23, 2021

Completed
27 days until next milestone

First Posted

Study publicly available on registry

December 20, 2021

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2026

Last Updated

May 1, 2025

Status Verified

April 1, 2025

Enrollment Period

4.8 years

First QC Date

November 23, 2021

Last Update Submit

April 28, 2025

Conditions

Keywords

spinal cord injurypaired brain and spinal cord stimulationconvergent stimulationspinal cord associative plasticitytranscutaneous spinal cord stimulationintraoperative monitoringupper-limb muscle activationmotor cortexcervical spinal cord

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    Immediately after SCAP

Secondary Outcomes (10)

  • Size of hand muscle response to spinal cord stimulation

    Immediately after SCAP

  • Duration of effect of SCAP on subsequent responses to brain or spinal cord stimulation

    1 hour after SCAP

  • Pinch force

    Immediately after SCAP

  • Amplitudes of H-reflex ratio

    Immediately after SCAP

  • Threshold for triggering muscle response from brain stimulation

    Immediately after SCAP

  • +5 more secondary outcomes

Study Arms (5)

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

EXPERIMENTAL

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

2. Intraoperative participants - Immediate effects of paired stimulation

EXPERIMENTAL

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 stimulationProcedure: Intraoperative pairing of cortical and spinal stimulation

3. Intraoperative participants - Lasting effects of SCAP

EXPERIMENTAL

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)

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

EXPERIMENTAL

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)

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

EXPERIMENTAL

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

Interventions

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.

1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulation2. Intraoperative participants - Immediate effects of paired 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.

2. Intraoperative participants - Immediate effects of paired 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.

1. Uninjured participants - Immediate and lasting effects of non-invasive paired stimulation3. Intraoperative participants - Lasting effects of SCAP4. Chronic cervical SCI participants - Lasting effects of non-invasive SCAP5. Intraoperative participants - Lasting effects of SCAP at or below myelopathic region

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.

3. Intraoperative participants - Lasting effects of SCAP

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

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

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (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.

You may not qualify if:

  • (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;
  • +12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Bronx Veterans Medical Research Foundation, Inc

New York, New York, 10029, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

QuadriplegiaSpinal Cord Injuries

Interventions

SREBP cleavage-activating protein

Condition Hierarchy (Ancestors)

ParalysisNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsSpinal Cord DiseasesCentral Nervous System DiseasesTrauma, Nervous SystemWounds and Injuries

Study Officials

  • Jason B Carmel, M.D., Ph.D.

    Columbia University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

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

CONTACT

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

November 23, 2021

First Posted

December 20, 2021

Study Start

September 10, 2021

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2026

Last Updated

May 1, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Within 6 months of manuscript preparation.
Access Criteria
Individually identifiable data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions described in the authorization and consent. A Data Use Agreement (DUA) will indicate adherence to any applicable Informed Consent provisions, and prohibits the recipient from identifying or re-identifying any individual whose data are included in the dataset.

Locations