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Activity-Dependent Transspinal Stimulation in SCI

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ClinicalTrials.gov Identifier: NCT03669302
Recruitment Status : Recruiting
First Posted : September 13, 2018
Last Update Posted : September 13, 2018
Sponsor:
Collaborator:
Bronx Veterans Medical Research Foundation, Inc
Information provided by (Responsible Party):
Maria Knikou, PT, PhD, City University of New York

Brief Summary:
Robotic gait training is often used with the aim to improve walking ability in individuals with Spinal Cord Injury. However, robotic gait training alone may not be sufficient. This study will compare the effects of robotic gait training alone to robotic gait training combined with either low-frequency or high-frequency non-invasive transspinal electrical stimulation. In people with motor-incomplete SCI, a series of clinical and electrical tests of nerve function will be performed before and after 20 sessions of gait training with or without stimulation.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Paraplegia, Spinal Tetraplegia/Tetraparesis Paraplegia, Spastic Other: Robotic gait training Device: Robotic gait training and low-frequency transspinal stimulation Device: Robotic gait training and high-frequency transspinal stimulation Not Applicable

Detailed Description:
People with spinal cord injury (SCI) have motor dysfunction that results in substantial social, personal, and economic costs. Robotic gait training is often used with the aim to improve walking ability in these individuals. Investigators recently reported that robotic gait training reorganizes spinal neuronal circuits, improves motor activity, and contributes substantially to recovery of walking ability in people with motor incomplete SCI. However, pathological muscle tone and abnormal muscle activation patterns during assisted stepping were still evident after multiple sessions of robotic gait training. Locomotor training alone may thus be insufficient to strengthen weak neuronal synapses connecting the brain with the spinal cord or to fully optimize spinal neural circuits. On the other hand, spinal cord stimulation increases sprouting and plasticity of axons and dendrites in spinalized animals. Furthermore, transcutaneous spinal cord stimulation (termed here transspinal stimulation) in people with SCI can evoke rhythmic leg muscle activity when gravity is eliminated. A fundamental knowledge gap still exists on induction of functional neuroplasticity and recovery of leg motor function after repetitive thoracolumbar transspinal stimulation during body weight supported (BWS) assisted stepping in people with SCI. The central working hypothesis in this study is that transspinal stimulation delivered during BWS-assisted stepping provides a tonic excitatory input increasing the overall responsiveness of the spinal cord and improving motor output. The investigators will address 3 specific aims: Establish induction of neuroplasticity and improvements in leg sensorimotor function in people with motor incomplete SCI when transspinal stimulation is delivered during BWS-assisted stepping at low frequencies (0.3 Hz; Specific Aim 1) and at high frequencies (30 Hz; Specific Aim 2), and when BWS-assisted step training is administered without transspinal stimulation (Specific Aim 3). In all groups, outcomes after 20 sessions will be measured via state-of-the-art neurophysiological methods. Corticospinal circuit excitability will be measured via transcranial magnetic stimulation motor evoked potentials in seated subjects (Aims 1A, 2A, 3A). Soleus H-reflex and tibialis anterior flexor reflex excitability patterns will be measured during assisted stepping (Aims 1B, 2B, 3B). Sensorimotor function will be evaluated via standardized clinical tests of gait and strength (Aims 1C, 2C, 3C). Additionally, poly-electromyographic analysis of coordinated muscle activation will be measured in detail. It is hypothesized that transspinal stimulation at 30 Hz during assisted stepping improves leg motor function and decreases ankle spasticity more compared to 0.3 Hz. It is further hypothesized that transspinal stimulation at 30 Hz normalizes the abnormal phase-dependent soleus H-reflex and flexor reflex modulation commonly observed during stepping in people with motor incomplete SCI. To test the project hypotheses, 45 people with motor incomplete SCI will be randomly assigned to receive 20 sessions of transspinal stimulation at 0.3 or 30 Hz during BWS-assisted stepping or 20 sessions of BWS-assisted stepping without transspinal stimulation (15 subjects per group). Results from this research project 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 improve leg motor function after motor incomplete SCI in humans.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Individuals with Spinal Cord Imjury will be randomly assigned to receive robotic gait training with the Lokomat, and/or Lokomat gait training combined with non-invasive thoracolumbar transspinal stimulation at 0.3 or at 30 Hz.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Activity-Dependent Transspinal Stimulation for Recovery of Walking Ability After Spinal Cord Injury
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : May 30, 2021
Estimated Study Completion Date : May 30, 2021


Arm Intervention/treatment
Sham Comparator: Robotic gait training
Robotic gait training only
Other: Robotic gait training
Fifteen people with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also non-invasive transspinal stimulation as a pulse train at 30 Hz 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: Robotic gait training & low-frequeny transspinal stimulation.
Robotic gait training will be administered along with non-invasive transspinal stimulation over the thoracolumbar region during assisted stepping at low frequency (0.3 Hz).
Device: Robotic gait training and low-frequency transspinal stimulation
Fifteen people with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also non-invasive transspinal stimulation as a single pulse at 0.3 Hz 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: Robotic gait training & high-frequeny transspinal stimulation.
Robotic gait training will be administered along with non-invasive transspinal stimulation over the thoracolumbar region during assisted stepping at high frequency (30 Hz).
Device: Robotic gait training and high-frequency transspinal stimulation
Fifteen people with spinal cord injury will receive 20 daily sessions of robotic gait training. During assisted stepping, they will receive also non-invasive transspinal stimulation as a pulse train at 30 Hz during the stance phase of gait. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.




Primary Outcome Measures :
  1. Plasticity of cortical and corticospinal neuronal 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.

  2. Plasticity of spinal neuronal circuits [ 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 and tibialis anterior flexor reflex.


Secondary Outcome Measures :
  1. Senorimotor leg motor function [ Time Frame: 3 years ]
    Manual muscle test and leg sensation based on American Spinal Injury Association guidelines.

  2. Spasticity [ Time Frame: 3 years ]
    Tardieu scale

  3. Walking function [ Time Frame: 3 years ]
    Two-minute walk test and 10 meter timed test.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 of the spine or spinal cord
  • Motor complete SCI
  • 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 stimulators
  • People with history of seizures
  • People with implanted Baclofen pumb

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03669302


Contacts
Contact: Maria Knikou, PT, PhD 17189823316 Maria.Knikou@csi.cuny.edu
Contact: Noam Y. Harel, MD, PhD 718-584-9000 ext 1742 noam.harel@mountsinai.org

Locations
United States, New York
Veterans Affairs Medical Center Recruiting
Bronx, New York, United States, 10468
Contact: Noam Y Harel, MD, PhD         
Department of Physical Therapy, Motor Control and NeuroRecovery Laboratory Recruiting
Staten Island, New York, United States, 10314
Contact: Maria Knikou, PT, PhD    718-982-3316    maria.knikou@csi.cuny.edu   
Sponsors and Collaborators
City University of New York
Bronx Veterans Medical Research Foundation, Inc
Investigators
Principal Investigator: Maria Knikou, PT, PhD Research Foundation of the City University of New York
Principal Investigator: Noam Y Harel, MD, PhD VA Office of Research and Development

Publications:

Responsible Party: Maria Knikou, PT, PhD, Professor, City University of New York
ClinicalTrials.gov Identifier: NCT03669302     History of Changes
Other Study ID Numbers: C33276GG
First Posted: September 13, 2018    Key Record Dates
Last Update Posted: September 13, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Maria Knikou, PT, PhD, City University of New York:
locomotor training
transcutaneous spinal cord stimulation
Lokomat
brain stimulation
peripheral nerve stimulation
H-reflex
spinal neural circuits
neuroplasticity
recovery

Additional relevant MeSH terms:
Spinal Cord Injuries
Quadriplegia
Paraplegia
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Paralysis
Neurologic Manifestations
Signs and Symptoms