Transspinal-Transcortical Paired Stimulation for Neuroplasticity and Recovery After SCI

November 11, 2020 updated by: College of Staten Island, the City University of New York
People with spinal cord injury (SCI) have motor dysfunction that results in substantial social, personal, and economic costs. Uncontrolled muscle spasticity and motor dysfunction result in disabilities that significantly reduce quality of life. Several rehabilitation interventions are utilized to treat muscle spasticity and motor dysfunction after SCI in humans. However, because most interventions rely on sensory afferent feedback that is interpreted by malfunctioned neuronal networks, rehabilitation efforts are greatly compromised. On the other hand, changes in the function of nerve cells connecting the brain and spinal cord have been reported following repetitive electromagnetic stimulation delivered over the head and legs or arms at specific time intervals. In addition, evidence suggests that electrical signals delivered to the spinal cord can regenerate spinal motor neurons in injured animals. A fundamental knowledge gap still exists on neuroplasticity and recovery of leg motor function in people with SCI after repetitive transspinal cord and transcortical stimulation. In this project, it is proposed that repetitive pairing of transspinal cord stimulation with transcortical stimulation strengthens the connections between the brain and spinal cord, decreases ankle spasticity, and improves leg movement. People with motor incomplete SCI will receive transspinal - transcortical paired associative stimulation at rest and during assisted stepping. The effects of this novel neuromodulation paradigm will be established via clinical tests and noninvasive neurophysiological methods that assess the pathways connecting the brain with the spinal cord.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Motor dysfunction after SCI results in substantial personal, social, and economic costs. Secondary complications related to muscle spasticity and motor dysfunction significantly reduce quality of life. Rehabilitation efforts are compromised because most therapeutic interventions rely heavily on sensory afferent feedback that is interpreted by malfunctioned neuronal networks. On the other hand, electrical signals delivered over the spine regenerate neurons of the spinal cord in injured animals, and paired associative stimulation produces enduring neuronal plasticity in healthy and injured humans and animals. A fundamental knowledge gap still exists on induction of functional neuroplasticity and recovery of leg motor function following repetitive pairing of transspinal cord stimulation with transcortical stimulation in people with motor incomplete SCI. Our central working hypothesis is that transspinal cord stimulation paired with transcortical stimulation strengthens corticospinal neuronal connections, decreases ankle spasticity, and improves leg motor function. This notion is based on the concept tested in the applicant's laboratory that this novel stimulation paradigm potentiates synaptic actions and activity of spared but compromised axons providing the necessary environment for functional neuroplasticity. The rationale of this research study is that neuromodulation methods that can modify effectively the input-output relations of cortical and spinal neuronal pathways in people with motor incomplete SCI are needed. Based on strong preliminary data, two specific aims will be addressed: Specific Aim 1: Establish induction of transspinal-transcortical paired associative stimulation (PAS) neuroplasticity and improvements in leg sensorimotor function in people with motor incomplete SCI when PAS is administered during robotic-assisted gait training. Cortical and corticospinal neuronal circuits via state-of-the-art neurophysiological methods in seated (Aim 1A), soleus H-reflex excitability during assisted stepping (Aim 1B), and sensorimotor function evaluated via standardized clinical tests (Aim 1C) will be assessed before and after 15 sessions of transspinal-transcortical PAS delivered with subjects supine. Specific Aim 2: Establish induction of transcortical-transspinal PAS neuroplasticity and improvements in leg sensorimotor function in people with motor incomplete SCI when PAS is administered during assisted stepping. Cortical and corticospinal neuroplasticity via state-of-the-art neurophysiological methods in seated (Aim 2A), soleus H-reflex excitability during assisted stepping (Aim 2B), and leg sensorimotor function evaluated via standardized clinical tests (Aim 2C) will be assessed before and after 15 sessions of transspinal-transcortical PAS delivered during assisted stepping. It is hypothesized that transspinal-transcortical PAS delivered at rest or during assisted stepping strengthens corticospinal connections, increases spinal inhibition, decreases ankle spasticity, and improves leg motor function. Further, transspinal-transcortical PAS delivered during assisted stepping normalizes the abnormal phase-dependent soleus H-reflex modulation commonly observed during stepping in people with motor incomplete SCI. To test the project hypotheses, 12 people with motor incomplete SCI will receive 20 sessions of transspinal-transcortical or transcortical-transspinal PAS during assisted stepping. In people with SCI, and assess improvements in leg motor function with standardized clinical tests. In all subjects, assessments of neuroplasticity in cortical, corticospinal, and spinal neuronal networks will be administered. These results will advance considerably the field of spinal cord research and change the standard of care because there is great potential for development of novel and effective rehabilitation strategies to manage spasticity and improve motor function after SCI in humans.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Staten Island, New York, United States, 10314
        • Department of Physical Therapy, College of Staten Island, City University of New York

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical diagnosis of motor incomplete spinal cord injury (SCI).
  • SCI is above thoracic 12 vertebra.
  • Absent permanent ankle joint contractures.
  • SCI occurred 6 months before enrollment to the study.

Exclusion Criteria:

  • Supraspinal lesions
  • Neuropathies of the peripheral nervous system
  • Degenerative neurological disorders
  • Presence of pressure sores
  • Urinary tract infection
  • Neoplastic or vascular disorders of the spine or spinal cord
  • Pregnant women or women who suspect they may be or may become pregnant
  • People with cochlear implants, pacemaker, and implanted simulators
  • People with history of seizures
  • People with implanted Baclofen pump

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Transspinal-transcortical paired-associative stimiulation combined with robotic gait training
Robotic gait training will be administered along with paired non-invasive transspinal stimulation over the thoracolumbar region and non-invasive brain stimulation during assisted stepping.
Device: Transspinal-transcortical paired-associative stimiulation combined with robotic gait training
Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive transspinal stimulation and non-invasive brain stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Experimental: Transcortical-transspinal paired-associative stimiulation combined with robotic gait training
Robotic gait training will be administered along with paired non-invasive brain stimulation and non-invasive transspinal stimulation over the thoracolumbar region during assisted stepping.
Device: Transcortical-transspinal paired-associative stimiulation combined with robotic gait training
Individuals with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also paired non-invasive brain stimulation and non-invasive transspinal stimulation during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasticity of cortical and corticospinal neural circuits
Time Frame: 3 years
Neurophysiological tests probing cortical and corticospinal excitability will be measured before and after the intervention. Single-pulse transcranial magnetic stimulation (TMS) will be used to assemble the recruitment curve of motor evoked potentials, and paired-pulse TMS will be used to probe changes in cortical inhibitory and facilitatory neuronal circuits.
3 years
Plasticity of spinal neural cicuits
Time Frame: 3 years
Neurophysiological tests probing spinal reflex excitability will be measured before and after each intervention by posterior tibial and sural nerves stimulation during Lokomat-assisted stepping depicting the amplitude modulation of the soleus H-reflex, tibialis anterior flexor reflex, and interlimb reflexes.
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sensorimotor leg motor function
Time Frame: 3 years
Manual muscle test and leg sensation based on American Spinal Injury Association
3 years
Walking function
Time Frame: 3 years
Two-minute walk test and 10 meter timed test
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
College of Staten Island, the City University of New York

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Maria Knikou, PT, PhD, College of Staten Island, City University of New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 5, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 10, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 3, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017-0261
  • C32095GG (Other Grant/Funding Number: New York State Department of Health Spinal Cord Injury Research Board)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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