Transspinal Stimulation Plus Locomotor Training for SCI

March 7, 2025 updated by: Maria Knikou, PT, PhD, City University of New York

Priming with High-Frequency Trans-spinal Stimulation to Augment Locomotor Benefits in Spinal Cord Injury

Locomotor training is often used with the aim to improve corticospinal function and walking ability in individuals with Spinal Cord Injury. Excitingly, the benefits of locomotor training may be augmented by noninvasive electrical stimulation of the spinal cord and enhance motor recovery at SCI. This study will compare the effects of priming locomotor training with high-frequency noninvasive thoracolumbar spinal stimulation. In people with motor-incomplete SCI, a series of clinical and electrical tests of brain and spinal cord function will be performed before and after 40 sessions of locomotor training where spinal stimulation is delivered immediately before either lying down or during standing.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Spinal cord injury (SCI) greatly impairs standing and walking ability, which severely compromises daily living activities. While these deficits are partially improved by locomotor training, even after multiple training sessions, abnormal muscle activity and coordination still persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits. As such, treatment interventions that effectively promote neuromodulation of spinal locomotor networks and strengthen neural connectivity of the injured human spinal cord in combination with physical rehabilitation are greatly needed. It is proposed that transcutaneous spinal cord (transspinal) stimulation as a method to synergistically 'prime' the nervous system to better respond to locomotor training. Transspinal stimulation alters motoneuron excitability over multiple spinal segments, a pre-requisite for functioning descending and local inputs. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after SCI is unknown. The goal of this clinical trial is to use high frequency (30 Hz) transspinal stimulation to prime locomotor training and ultimately improve standing, walking, and overall function in individuals with chronic incomplete SCI (iSCI). Forty-five individuals with iSCI will undergo 40 sessions of body weight-supported step training primed with high-frequency transspinal stimulation. Participants will be randomized to receive transspinal stimulation during standing (real or sham) or while supine (real). Aim 1 evaluates how priming locomotor training with high-frequency transspinal stimulation in SCI alters corticomotoneuronal connectivity strength, as indicated by motor evoked potentials recorded from the legs.

Aim 2 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI affects reorganization and appropriate engagement of spinal neuronal circuits. Finally, Aim 3 evaluates activity-based motor function, ability to stand and walk, and quality of life. These results will support the notion that tonic high-frequency transspinal stimulation strengthens corticomotoneuronal connectivity and improves spinal circuit organization through posture-dependent corticospinal neuroplasticity. It is anticipated that the information gained from this mechanistic clinical trial will greatly impact clinical practice. This is because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • 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
      • Bronx, New York, United States, 10468
        • Veterans Affairs Medical Center
      • Staten Island, New York, United States, 10314
        • Department of Physical Therapy, Motor Control and NeuroRecovery Laboratory

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

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Willingness to comply with all study procedures and availability for the duration of the study.
  • Ability to understand the consent form, and sign the consent form.
  • Male or female, age 18-70 years old.
  • In good general health as evidenced by medical history.
  • Diagnosed with motor incomplete SCI (AIS C-D).
  • Bone mineral density of the hip (proximal femur) T-score <3.5 SD from age- and gender-matched normative data.
  • Lesion above thoracic (T) 10 to ensure absent lower motoneuron lesion.
  • Presence of tendon reflexes to be able to elicit the soleus H-reflex.
  • Absent permanent ankle joint contractures that prevent passive or active ankle movement because corticospinal and spinal excitability is based on the ankle angle. The ankle straps of the Lokomat require also flexible ankle joints.
  • A diagnosis of first time SCI due to trauma, vascular, or orthopedic pathology.
  • Time after SCI of more than 6 months.
  • Stable medical condition without cardiopulmonary disease or cognitive impairment.

Exclusion Criteria:

  • Supraspinal lesions.
  • Significant neuropathies of the peripheral nervous system.
  • Significant degenerative neurological disorders of the spine or spinal cord.
  • AIS A or B.
  • Presence of pressure sores.
  • Advanced urinary tract infection.
  • Neoplastic or vascular disorders of the spine or spinal cord.
  • Participation in an ongoing research study or new rehabilitation program.
  • Pregnant women or women who suspect they may be, or may become pregnant will be excluded from participation because the risks of thoracolumbar stimulation to the fetus are unknown.
  • People with cochlear implants, pacemaker, implanted infusion device, and/or implanted stimulators of any type and purpose will be excluded to avoid their malfunction due to stimulation.
  • People with history of seizures.
  • Medical conditions that increase the possibility of seizures.
  • Medications that may change the seizure threshold.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Real transspinal stimulation delivered during standing followed by locomotor training
Transspinal tonic stimulation of the thoracolumbar region will be delivered at a frequency of 30 Hz during standing with as needed body weight support (BWS) in a standing frame or in the Lokomat to ensure safety.
Combination product: Standing transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation during standing followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Other Names:
  • Standing transspinal stimulation
Experimental: Real transspinal stimulation delivered while lying supine followed by locomotor training
Transspinal tonic stimulation will be delivered at a frequency of 30 Hz while lying supine.
Combination product: Lying transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation while lying supine on a therapy table followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Other Names:
  • Lying transspinal stimulation
Sham Comparator: Sham transspinal stimulation delivered during standing followed by locomotor training
One sham group will be receiving transspinal stimulation during standing at an intensity where sensation is absent.
Other: Standing sham transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of sham transspinal stimulation during standing at an intensity where sensation is absent followed by 30 minutes of robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Other Names:
  • Robotic gait training

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasticity of spinal neuronal networks
Time Frame: 4 years
Neurophysiological assessments probing changes in excitatory and inhibitory spinal reflex excitability from interventions by recording amplitude modulation of the soleus H-reflex following posterior tibial and common peroneal nerves stimulation both at rest and during robotic-assisted stepping.
4 years
Plasticity of corticospinal networks
Time Frame: 4 years
Neurophysiological measurements assessing changes in corticospinal excitability from the interventions by recording responses to single-pulse transcranial magnetic stimulation (TMS) at rest and during robotic-assisted stepping.
4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ambulatory function
Time Frame: 4 years
Change in two-minute walk and 10-meter timed test.
4 years
Balance
Time Frame: 4 years
Changes in BESTtest clinical assessments.
4 years
Autonomic function
Time Frame: 4 years
Questionnaire assessing participants perceived changes in bowel, bladder, and sexual function
4 years

Collaborators and Investigators

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

Sponsor

City University of New York

Collaborators

Icahn School of Medicine at Mount Sinai
Bronx Veterans Medical Research Foundation, Inc

Investigators

  • Principal Investigator: Noam Y. Harel, MD, PhD, Bronx Veterans Medical Research Foundation
  • Principal Investigator: Maria Knikou, PT, PhD, Research Foundation of the 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)

August 1, 2021

Primary Completion (Actual)

December 1, 2024

Study Completion (Actual)

December 31, 2024

Study Registration Dates

First Submitted

March 11, 2021

First Submitted That Met QC Criteria

March 18, 2021

First Posted (Actual)

March 19, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 7, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01HD100544 (U.S. NIH Grant/Contract)

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

product manufactured in and exported from the U.S.

No

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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