Harnessing Neuroplasticity of Postural Sensorimotor Networks Using Non-Invasive Spinal Neuromodulation to Maximize Functional Recovery After Spinal Cord Injury

March 25, 2026 updated by: sayenko dimitry, The Methodist Hospital Research Institute
It has been demonstrated that the human lumbosacral spinal cord can be neuromodulated with epidural (ESS) and transcutaneous (TSS) spinal cord stimulation to enable recovery of standing and volitional control of the lower limbs after complete motor paralysis due to spinal cord injury (SCI). The work proposed herein will examine and identify distinct electrophysiological mechanisms underlying transcutaneous spinal stimulation (TSS) and epidural spinal stimulation (ESS) to define how these approaches determine the ability to maintain self-assisted standing after SCI.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Spinal circuitries below a paralyzing injury have a functional potential that far exceeds what has been thought possible. It has been demonstrated that task-specific motor therapy combined with epidural spinal cord stimulation (ESS) can promote improved motor function during postural, locomotor, and voluntary movement tasks, resulting in dramatic effects on the wellbeing of individuals with spinal cord injury (SCI). While these findings indicate a substantial promise for restoring mobility even after motor complete paralysis, chronic ESS is based on a high-cost implantable device, as well as an expensive and invasive surgical procedure. The investigators have developed a cost-effective alternative to ESS - non-invasive, transcutaneous electrical stimulation of the spinal cord (TSS). Preliminary works demonstrate that this neuromodulatory strategy provides sufficient specificity to selectively stimulate multisegmental dorsal nerve roots, enable stepping movements, and improve postural control during sitting and standing in individuals with motor complete SCI. The similarities between the effects of ESS and TSS are of critical importance in guiding more individually-specific neuromodulatory approaches to improve motor function and mobility after SCI, but have not been compared directly in the same subjects.

This study is focused on investigation the effects and mechanisms of each spinal neuromodulation strategy in regaining self-assisted standing. Not only is the recovery of balance control one of the most desired goals of people with paralysis, it provides the foundation necessary for regaining the ability to walk, and is critical to future therapies, involving robotic (e.g. exoskeleton) technologies. The objectives of this study are (1) to define the therapeutic potential of TSS during standing in individuals with motor complete SCI, and (2) to identify the neurophysiological and functional signatures of TSS and ESS. The central hypothesis is that each of the neuromodulatory strategies, when individually tailored, can result in significant motor recovery in individuals with chronic paralysis by reactivation and integration of networks that were clinically dormant prior to the intervention. The investigators predict that this proposal will have a high impact given that it encompasses multiple functional systems that contribute to the independence and quality of life in a broad population of individuals with SCI, and provides the first direct comparison of the invasive and non-invasive approaches. The investigators propose a progressive, mechanistic, and translational study to validate the effects of each approach, examine the neuroplastic capacity caused by activity-based training in the presence of TSS, and evaluate TSS and ESS stimulation paradigms as rehabilitative modalities after SCI.

Study Type

Interventional

Enrollment (Estimated)

60

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 Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Dimitry Sayenko, MD, PhD

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. All participants must be able to provide a provision of a signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Male or female, aged 22-75 years old.
  4. Documentation from the participant's primary treating physician confirming a stable medical condition.
  5. Inability to maintain standing independently without external support due to SCI AIS A-C.
  6. Ability to tolerate at least 15 minutes in an upright (supported) position.
  7. Able to self-transfer from the wheelchair and demonstrate active range of motion of bilateral upper extremities in gravity dependent plane.

  8. Able to passively range bilateral lower extremities within normal mobility parameters including:

    1. greater than 90 degrees of hip flexion and 165 degrees of hip extension;
    2. greater than 90 degrees of knee flexion and reach neutral knee extension of 180 degrees;
    3. neutral ankle position reaching a minimum of 90 degrees of dorsiflexion.
  9. Participants should be on a stable intrathecal baclofen or oral anti-spasticity regimen/dose for the period of the study unless advised otherwise by their physician.
  10. 1 to 30 years post spinal cord injury.
  11. Non-progressive spinal cord injury.
  12. Neurological level of injury below C4 and above T12 (excluding conus injury and/or indications of lower motor neuron injury).
  13. Eligible for fMRI per safety questionnaire.
  14. Women of childbearing potential must agree to the use of an effective means of avoiding pregnancy for the duration of the study.
  15. Able to commit to the full study.

Exclusion Criteria:

  1. Ability to maintain standing independently without external support.
  2. Currently involved in another rehabilitation training of the lower extremities.
  3. Active pressure sores, unhealed bone fractures, peripheral neuropathies, or painful musculoskeletal dysfunction (including but not limited to contractures in the upper and lower extremities).
  4. Any ongoing medical condition which would preclude participant from regular physical activity (including but not limited to: cardiopulmonary disease, uncontrollable autonomic dysreflexia or orthostatic hypotension, active urinary tract infections, pregnant or nursing).
  5. Intrathecal baclofen pump therapy for spasticity not compatible with 3T MRI.
  6. Must not have received Botox injections to primary lower extremity and trunk musculature within the past 3 months, resulting in absence of muscle tone and precluding response to electrical stimulation therapy.
  7. Current or history of neuromuscular conditions (including but not limited to: unhealed ligament of muscular tears in the upper or lower extremities, pain in weight bearing positions for upper and lower extremities).
  8. Clinically significant depression, psychiatric disorders, or ongoing drug abuse, including heavy alcohol use.
  9. Any reason the PI or treating physician may deem as harmful to the participant to enroll or continue in the study.
  10. Body Mass Index (BMI) over 30.
  11. Pregnancy.
  12. Use a ventilator or diaphragmatic pacer.

  13. Participants with the following conditions will be excluded from TMS, but may take part in the overall study:

    • Personal or first-degree family history of seizures or epilepsy.
    • Metal in the head, except mouth implants.
    • History of suicide attempts.
    • History of intracranial lesions, increased intracranial pressure, or stroke.
    • Current use of tricyclic anti-depressants, selective serotonin reuptake inhibitors (SSRIs), serotonin nor-epinephrine reuptake inhibitors (SNRIs), buproprion (Wellbutrin), or tramadol.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Transcutaneous Spinal Stimulation (TSS)
Spinal Stimulation delivered over the skin using a research stimulator with conventional surface electrodes during research visits.
Device: Transcutaneous Spinal cord Stimulation
Delivered using a constant-current stimulator
Experimental: Epidural Spinal Stimulation (ESS)
Stimulation delivered internally using an implanted device operated by an external control (only used during research visits).
Device: Epidural Spinal Stimulation (ESS)

The device used for ESS, the CoverEdgeX 32 Surgical Lead system (Boston Scientific, USA), is a device approved by the FDA used in the treatment of severe pain and is approved for individuals to manage chronic pain when other treatments have not been effective.

If you are in the ESS group, you will have surgery to have the stimulator placed and the stimulator will be removed at an office visit towards the end of the study.
Sham Comparator: Sham
Sham Stimulation delivered over the skin using a research stimulator with conventional surface electrodes during research visits. Sham stimulation will be delivered using the intensity of stimulation set as during active sessions of ESS, but then gradually decreased down to zero in approximately 30 s. There will be 5-10 minute breaks interspersed between intervals of stimulation, and will vary according to the individual's tolerance and fatigue levels
Device: Transcutaneous Spinal cord Stimulation
Delivered using a constant-current stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of force generation by lower limbs
Time Frame: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)
Neuromotor outcomes will be assessed during supine and upright standing, focusing on leg extension force output. Measurements will be taken under various conditions, including voluntary effort without spinal stimulation, and in the presence of Transcutaneous Spinal Stimulation (TSS), Epidural Spinal Stimulation (ESS), or Sham stimulation. The force output will be quantified in newtons (N). The magnitude of EMG signals will be quantified and expressed in millivolts (mV).
Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of neurological status
Time Frame: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)
International Standards for Neurological Classification of SCI (ISNCSCI). The total motor score has a range of 0 to 100, with specific key muscles assessed on both sides of the body. The sensory scores also range from 0 to 112, evaluating light touch and pinprick sensation in different dermatomes.
Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)
Assessment of Independence
Time Frame: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)
Spinal Cord Independence Measure (SCIM). The SCIM involves assessing various neurological functions and assigning scores. The SCIM has a scale ranging from 0 to 100, with higher scores indicating greater independence in activities of daily living. The minimum score signifies complete dependence, while the maximum score reflects complete independence.
Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Collaborators and Investigators

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

Sponsor

The Methodist Hospital Research Institute

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Dimitry Sayenko, MD, PhD, The Methodist Hospital Research Institute

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)

December 6, 2023

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2027

Study Registration Dates

First Submitted

October 26, 2023

First Submitted That Met QC Criteria

January 8, 2024

First Posted (Actual)

January 19, 2024

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 25, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO00037483
  • 5R01NS119587-02 (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

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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