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Spinal Cord InjuriesNCT06213012

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

A study testing Transcutaneous Spinal cord Stimulation and Epidural Spinal Stimulation (ESS) in people with Spinal Cord Injuries and Neuromodulation, run by The Methodist Hospital Research Institute at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 22 to 75 years
Conditions the study is for
Spinal Cord Injuries, Neuromodulation
What is being tested?
Transcutaneous Spinal cord Stimulation and Epidural Spinal Stimulation (ESS)
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited States
Study dates
6 Dec 2023to 31 Aug 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 22 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All participants must be able to provide a provision of a signed and dated informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Male or female, aged 22-75 years old.
  • Documentation from the participant's primary treating physician confirming a stable medical condition.
  • Inability to maintain standing independently without external support due to SCI AIS A-C.
  • Ability to tolerate at least 15 minutes in an upright (supported) position.
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  • Able to self-transfer from the wheelchair and demonstrate active range of motion of bilateral upper extremities in gravity dependent plane.
  • Able to passively range bilateral lower extremities within normal mobility parameters including:
  • greater than 90 degrees of hip flexion and 165 degrees of hip extension;
  • greater than 90 degrees of knee flexion and reach neutral knee extension of 180 degrees;
  • neutral ankle position reaching a minimum of 90 degrees of dorsiflexion.
  • 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.
  • 1 to 30 years post spinal cord injury.
  • Non-progressive spinal cord injury.
  • Neurological level of injury below C4 and above T12 (excluding conus injury and/or indications of lower motor neuron injury).
  • Eligible for fMRI per safety questionnaire.
  • Women of childbearing potential must agree to the use of an effective means of avoiding pregnancy for the duration of the study.
  • Able to commit to the full study.

Who cannot join

  • Ability to maintain standing independently without external support.
  • Currently involved in another rehabilitation training of the lower extremities.
  • Active pressure sores, unhealed bone fractures, peripheral neuropathies, or painful musculoskeletal dysfunction (including but not limited to contractures in the upper and lower extremities).
  • 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).
  • Intrathecal baclofen pump therapy for spasticity not compatible with 3T MRI.
  • 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.
Show all 18Show fewer
  • 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).
  • Clinically significant depression, psychiatric disorders, or ongoing drug abuse, including heavy alcohol use.
  • Any reason the PI or treating physician may deem as harmful to the participant to enroll or continue in the study.
  • Body Mass Index (BMI) over 30.
  • Pregnancy.
  • Use a ventilator or diaphragmatic pacer.
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jenny Dinh, BS contact

585-507-1706

jtdinh@houstonmethodist.org

Amanda Howes-Keith, MS contact

585-507-1706

achowes-keith@houstonmethodist.org

United States1 site, 1 recruiting

  • Houston Methodist Hospital

    Houston, Texas, 77030

    Jenny Dinh, (346)-238-4654, jtdinh@houstonmethodist.org

    Dimitry Sayenko, MD, PhD

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Being tested
Transcutaneous Spinal cord Stimulation, Epidural Spinal Stimulation (ESS)
Medical subject headings
Spinal Cord Injuries

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Transcutaneous Spinal cord StimulationDevice

    Delivered using a constant-current stimulator

  • Epidural Spinal Stimulation (ESS)Device

    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.

Study groups in NCT06213012
Study groupRoleWhat they receive
Transcutaneous Spinal Stimulation (TSS)Active comparatorSpinal Stimulation delivered over the skin using a research stimulator with conventional surface electrodes during research visits.
Receives: Device: Transcutaneous Spinal cord Stimulation
ShamSham comparatorSham 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
Receives: Device: Transcutaneous Spinal cord Stimulation
Epidural Spinal Stimulation (ESS)ExperimentalStimulation delivered internally using an implanted device operated by an external control (only used during research visits).
Receives: Device: Epidural Spinal Stimulation (ESS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of force generation by lower limbs

    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).

    Measured: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Secondary outcomes (2)

  1. Assessment of neurological status

    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.

    Measured: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

  2. Assessment of Independence

    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.

    Measured: Baseline 1(week 1), baseline 2(week 6), post interventions (week 11), and follow up (week 16)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2024
  2. Study start6 Dec 2023
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
optional crossover arm for returning participants.
Masking
Single blind
Who is masked
Participant
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06213012
Sponsor's protocol ID
PRO00037483
Other IDs
5R01NS119587-02
Status last verified
Mar 2026
First submitted
26 Oct 2023
Last updated
30 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Biering-Sorensen F, Hansen B, Lee BS. Non-pharmacological treatment and prevention of bone loss after spinal cord injury: a systematic review. Spinal Cord. 2009 Jul;47(7):508-18. doi: 10.1038/sc.2008.177. Epub 2009 Jan 27.

    PubMed 19172152

  • Harkema SJ, Ferreira CK, van den Brand RJ, Krassioukov AV. Improvements in orthostatic instability with stand locomotor training in individuals with spinal cord injury. J Neurotrauma. 2008 Dec;25(12):1467-75. doi: 10.1089/neu.2008.0572.

    PubMed 19118454

  • Agarwal S, Triolo RJ, Kobetic R, Miller M, Bieri C, Kukke S, Rohde L, Davis JA Jr. Long-term user perceptions of an implanted neuroprosthesis for exercise, standing, and transfers after spinal cord injury. J Rehabil Res Dev. 2003 May-Jun;40(3):241-52.

    PubMed 14582528

  • Walter JS, Sola PG, Sacks J, Lucero Y, Langbein E, Weaver F. Indications for a home standing program for individuals with spinal cord injury. J Spinal Cord Med. 1999 Fall;22(3):152-8. doi: 10.1080/10790268.1999.11719564.

    PubMed 10685379

  • Fernhall B, Heffernan K, Jae SY, Hedrick B. Health implications of physical activity in individuals with spinal cord injury: a literature review. J Health Hum Serv Adm. 2008 Spring;30(4):468-502.

    PubMed 18236700

  • Anneken V, Hanssen-Doose A, Hirschfeld S, Scheuer T, Thietje R. Influence of physical exercise on quality of life in individuals with spinal cord injury. Spinal Cord. 2010 May;48(5):393-9. doi: 10.1038/sc.2009.137. Epub 2009 Oct 20.

    PubMed 19841634

  • Snoek GJ, IJzerman MJ, Hermens HJ, Maxwell D, Biering-Sorensen F. Survey of the needs of patients with spinal cord injury: impact and priority for improvement in hand function in tetraplegics. Spinal Cord. 2004 Sep;42(9):526-32. doi: 10.1038/sj.sc.3101638.

    PubMed 15224087

  • Sayenko DG, Rath M, Ferguson AR, Burdick JW, Havton LA, Edgerton VR, Gerasimenko YP. Self-Assisted Standing Enabled by Non-Invasive Spinal Stimulation after Spinal Cord Injury. J Neurotrauma. 2019 May 1;36(9):1435-1450. doi: 10.1089/neu.2018.5956. Epub 2018 Dec 15.

    PubMed 30362876

  • Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Nov;24(11):1677-1682. doi: 10.1038/s41591-018-0175-7. Epub 2018 Sep 24.

    PubMed 30250140

  • Grahn PJ, Lavrov IA, Sayenko DG, Van Straaten MG, Gill ML, Strommen JA, Calvert JS, Drubach DI, Beck LA, Linde MB, Thoreson AR, Lopez C, Mendez AA, Gad PN, Gerasimenko YP, Edgerton VR, Zhao KD, Lee KH. Enabling Task-Specific Volitional Motor Functions via Spinal Cord Neuromodulation in a Human With Paraplegia. Mayo Clin Proc. 2017 Apr;92(4):544-554. doi: 10.1016/j.mayocp.2017.02.014.

    PubMed 28385196

  • Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24.

    PubMed 30247091

  • Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014 May;137(Pt 5):1394-409. doi: 10.1093/brain/awu038. Epub 2014 Apr 8.

    PubMed 24713270

  • Munoz Perez M, Cortes Velasco M, Martinez Elizondo G, Guitron Cantu A, Contreras Soto J, Forsbach Sanchez G. [Ovulation induction in normoprolactinemic anovulatory patients with bromocriptine and clomiphene citrate]. Ginecol Obstet Mex. 1988 Sep;56:256-62. No abstract available. Spanish.

    PubMed 3154251

  • Rossignol S, Frigon A. Recovery of locomotion after spinal cord injury: some facts and mechanisms. Annu Rev Neurosci. 2011;34:413-40. doi: 10.1146/annurev-neuro-061010-113746.

    PubMed 21469957

  • Campbell WW, Sahni SK, Pridgeon RM, Riaz G, Leshner RT. Intraoperative electroneurography: management of ulnar neuropathy at the elbow. Muscle Nerve. 1988 Jan;11(1):75-81. doi: 10.1002/mus.880110112.

    PubMed 2828944

Questions about this trial

What is this clinical trial studying?

A study testing Transcutaneous Spinal cord Stimulation and Epidural Spinal Stimulation (ESS) in people with Spinal Cord Injuries and Neuromodulation, run by The Methodist Hospital Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jenny Dinh, BS (585-507-1706, jtdinh@houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06213012, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.

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