Spinal Cord InjuriesNCT04807764
Transspinal Stimulation Plus Locomotor Training for SCI
A study testing Standing transspinal stimulation followed by robotic gait training and Lying transspinal stimulation followed by robotic gait training in people with Spinal Cord Injuries and Paraplegia, Spinal, run by City University of New York at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Spinal Cord Injuries, Paraplegia, Spinal, Tetraplegia/Tetraparesis
- What is being tested?
- Standing transspinal stimulation followed by robotic gait training and Lying transspinal stimulation followed by robotic gait training
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Aug 2021to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Department of Physical Therapy, Motor Control and NeuroRecovery Laboratory
Staten Island, New York, 10314
Veterans Affairs Medical Center
The Bronx, New York, 10468
About this study
Official title: 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.
Read the 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.
- Being tested
- Standing transspinal stimulation followed by robotic gait training, Lying transspinal stimulation followed by robotic gait training, Standing sham transspinal stimulation followed by robotic gait training
- Keywords
- Locomotor Training, Transcutaneous Spinal Cord Stimulation, Lokomat, Peripheral Nerve Stimulation, H-Reflex, Spinal Neural Circuits, Neuroplasticity, Recovery
- Medical subject headings
- Spinal Cord Injuries, Paraplegia, Quadriplegia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standing transspinal stimulation followed by robotic gait trainingCombination product
Also called Standing transspinal stimulation
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.
Lying transspinal stimulation followed by robotic gait trainingCombination product
Also called Lying transspinal stimulation
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.
Standing sham transspinal stimulation followed by robotic gait trainingOther
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Real transspinal stimulation delivered during standing followed by locomotor training | Experimental | 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. Receives: Combination Product: Standing transspinal stimulation followed by robotic gait training |
| Real transspinal stimulation delivered while lying supine followed by locomotor training | Experimental | Transspinal tonic stimulation will be delivered at a frequency of 30 Hz while lying supine. Receives: Combination Product: Lying transspinal stimulation followed by robotic gait training |
| Sham transspinal stimulation delivered during standing followed by locomotor training | Sham comparator | One sham group will be receiving transspinal stimulation during standing at an intensity where sensation is absent. Receives: Other: Standing sham transspinal stimulation followed by robotic gait training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasticity of Spinal Neuronal Networks - Homosynaptic Depression
Soleus H-reflexes following posterior tibial nerve stimulation with a 1-ms monophasic pulse were recorded with subjects seated and stimuli delivered every 1 s (1.0 Hz), 3 s (0.33 Hz), 5 s (0.2 Hz), 8 s (0.125 Hz), and 10s (0.1 Hz). Results for each interval vs 0.1 Hz shown.
Measured: 4-6 months
Plasticity of Spinal Neuronal Networks - Presynaptic Inhibition
Presynaptic inhibition was assessed with a conditioning pulse train of 4 pulses with 9 ms duration, delivered to the CPN at the C-T intervals of 20, 60, or 100 ms. These C-T intervals were selected because the reflex inhibition produced at the intermediate C-T intervals is predominantly presynaptic. The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively. Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged.
Results are listed for each C-T interval, pre- and post-intervention.
Measured: 4-6 months
Plasticity of Spinal Neuronal Networks - Reciprocal Inhigition
To assess restoration of reciprocal Ia inhibition, soleus H-reflexes were recorded following common peroneal nerve (CPN) stimulation at short conditioning-test (C-T) intervals of 0, 1, 2, 3, and 4 ms.
The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively.
Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged.
Results are listed for each C-T interval, pre- and post-intervention.
Measured: 4-6 months
Plasticity of Corticospinal Networks
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.
The tibialis anterior resting motor threshold (RMT) was established and corresponded to the lowest TMS maximal stimulator output that induced reproducible evoked potentials of at least ~50 µV in 4 out of 5 consecutive single TMS pulses.
RMTs (percentage of maximal stimulator output) are shown pre- and post-intervention.
Measured: 4-6 months
Secondary outcomes (3)
Ambulatory Function
Change in 10-meter timed test (seconds required to complete 10-meter walk) between baseline and post-intervention. Fewer seconds means faster (better) gait.
Measured: 4-6 months
Balance
Changes in Berg Balance Scale score between baseline and post-intervention. Scale scores between 0 and 56. Higher scores mean better balance.
Measured: 4-6 months
Autonomic Function
SCIM III Bladder and Bowel management subscores Bladder subscore rated 0-15 (higher means better bladder function). Bowel subscore rated 0-10 (higher means better bowel function).
Measured: 4-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start1 Aug 2021
- Primary completion1 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (142)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- This is a mechanistic randomized clinical trial. We will enroll 45 individuals with SCI. We will use blocked randomization into three groups with a block size of nine, with stratification according to severity of SCI (ambulatory with assistive device, or not ambulatory).1 We will check after completion of intervention by all subjects in each group whether the groups are balanced or not regarding baseline motor function and perform tests of association accordingly.
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- City University of New York
- Sponsor type
- University, hospital or other
- Collaborators
- Bronx Veterans Medical Research Foundation, Inc, Icahn School of Medicine at Mount Sinai
- Responsible party
- Principal investigator, Maria Knikou, PT, MBA, PhD, City University of New York
- Investigators
- Maria Knikou, PT, PhD, Principal investigator, Research Foundation of the City University of New YorkNoam Y. Harel, MD, PhD, Principal investigator, Bronx Veterans Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807764
- Sponsor's protocol ID
- R01HD100544
- Status last verified
- Jul 2026
- First submitted
- 11 Mar 2021
- Last updated
- 18 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
Cote MP, Murray LM, Knikou M. Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions. Front Physiol. 2018 Jun 25;9:784. doi: 10.3389/fphys.2018.00784. eCollection 2018.
PubMed 29988534Ellaway PH, Catley M, Davey NJ, Kuppuswamy A, Strutton P, Frankel HL, Jamous A, Savic G. Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes. J Rehabil Res Dev. 2007;44(1):69-76. doi: 10.1682/jrrd.2005.08.0140.
PubMed 17551860Wirth B, van Hedel HJ, Curt A. Ankle paresis in incomplete spinal cord injury: relation to corticospinal conductivity and ambulatory capacity. J Clin Neurophysiol. 2008 Aug;25(4):210-7. doi: 10.1097/WNP.0b013e318183f4e3.
PubMed 18677185Cirillo J, Calabro FJ, Perez MA. Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury. Cereb Cortex. 2016 May;26(5):2167-77. doi: 10.1093/cercor/bhv048. Epub 2015 Mar 25.
PubMed 25814508Arvanian VL, Schnell L, Lou L, Golshani R, Hunanyan A, Ghosh A, Pearse DD, Robinson JK, Schwab ME, Fawcett JW, Mendell LM. Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons. Exp Neurol. 2009 Apr;216(2):471-80. doi: 10.1016/j.expneurol.2009.01.004.
PubMed 19320005Nielsen JB, Crone C, Hultborn H. The spinal pathophysiology of spasticity--from a basic science point of view. Acta Physiol (Oxf). 2007 Feb;189(2):171-80. doi: 10.1111/j.1748-1716.2006.01652.x.
PubMed 17250567Knikou M. Plantar cutaneous input modulates differently spinal reflexes in subjects with intact and injured spinal cord. Spinal Cord. 2007 Jan;45(1):69-77. doi: 10.1038/sj.sc.3101917. Epub 2006 Mar 14.
PubMed 16534501Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Soleus H-reflex gain, threshold, and amplitude as function of body posture and load in spinal cord intact and injured subjects. Int J Neurosci. 2009;119(11):2056-73. doi: 10.1080/00207450903139747.
PubMed 19863261Knikou M, Angeli CA, Ferreira CK, Harkema SJ. Soleus H-reflex modulation during body weight support treadmill walking in spinal cord intact and injured subjects. Exp Brain Res. 2009 Mar;193(3):397-407. doi: 10.1007/s00221-008-1636-x. Epub 2008 Nov 15.
PubMed 19011843Barthelemy D, Willerslev-Olsen M, Lundell H, Biering-Sorensen F, Nielsen JB. Assessment of transmission in specific descending pathways in relation to gait and balance following spinal cord injury. Prog Brain Res. 2015;218:79-101. doi: 10.1016/bs.pbr.2014.12.012. Epub 2015 Mar 29.
PubMed 25890133Barthelemy D, Willerslev-Olsen M, Lundell H, Conway BA, Knudsen H, Biering-Sorensen F, Nielsen JB. Impaired transmission in the corticospinal tract and gait disability in spinal cord injured persons. J Neurophysiol. 2010 Aug;104(2):1167-76. doi: 10.1152/jn.00382.2010. Epub 2010 Jun 16.
PubMed 20554839James ND, McMahon SB, Field-Fote EC, Bradbury EJ. Neuromodulation in the restoration of function after spinal cord injury. Lancet Neurol. 2018 Oct;17(10):905-917. doi: 10.1016/S1474-4422(18)30287-4. Epub 2018 Sep 18.
PubMed 30264729Tansey KE, McKay WB, Kakulas BA. Restorative neurology: consideration of the new anatomy and physiology of the injured nervous system. Clin Neurol Neurosurg. 2012 Jun;114(5):436-40. doi: 10.1016/j.clineuro.2012.01.010. Epub 2012 Feb 1.
PubMed 22300890Smith AC, Mummidisetty CK, Rymer WZ, Knikou M. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury. J Neurophysiol. 2014 Nov 1;112(9):2164-75. doi: 10.1152/jn.00308.2014. Epub 2014 Aug 13.
PubMed 25122715Smith AC, Rymer WZ, Knikou M. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury. Exp Brain Res. 2015 Jan;233(1):89-103. doi: 10.1007/s00221-014-4094-7. Epub 2014 Sep 10.
PubMed 25205562
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Priming With High-Frequency Trans-spinal Stimulation to Augment Locomotor Benefits in Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT04807764
- Acronym / sponsor ID
- R01HD100544
- Keywords
- Locomotor Training, Transcutaneous Spinal Cord Stimulation, Lokomat, Peripheral Nerve Stimulation, H-Reflex, Spinal Neural Circuits, Neuroplasticity, Recovery
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- City University of New YorkUniversity, hospital or other
- Collaborators
- Bronx Veterans Medical Research Foundation, Inc, Icahn School of Medicine at Mount Sinai
- Study start
- 1 Aug 2021 (actual)
- Primary completion
- 1 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 19 Mar 2021 (actual)
- Results
- Posted 18 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a mechanistic randomized clinical trial. We will enroll 45 individuals with SCI. We will use blocked randomization into three groups with a block size of nine, with stratification according to severity of SCI (ambulatory with assistive device, or not ambulatory).1 We will check after completion of intervention by all subjects in each group whether the groups are balanced or not regarding baseline motor function and perform tests of association accordingly.
| Arm | Type | Receives |
|---|---|---|
| Real transspinal stimulation delivered during standing followed by locomotor training | Experimental | Combination Product: Standing transspinal stimulation followed by robotic gait trainingTransspinal 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. |
| Real transspinal stimulation delivered while lying supine followed by locomotor training | Experimental | Combination Product: Lying transspinal stimulation followed by robotic gait trainingTransspinal tonic stimulation will be delivered at a frequency of 30 Hz while lying supine. |
| Sham transspinal stimulation delivered during standing followed by locomotor training | Sham comparator | Other: Standing sham transspinal stimulation followed by robotic gait trainingOne sham group will be receiving transspinal stimulation during standing at an intensity where sensation is absent. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standing transspinal stimulation followed by robotic gait trainingAlso: Standing transspinal stimulationFifteen 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. | Combination product | Real transspinal stimulation delivered during standing followed by locomotor training |
| Lying transspinal stimulation followed by robotic gait trainingAlso: Lying transspinal stimulationFifteen 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. | Combination product | Real transspinal stimulation delivered while lying supine followed by locomotor training |
| Standing sham transspinal stimulation followed by robotic gait trainingAlso: Robotic gait trainingFifteen 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 | Sham transspinal stimulation delivered during standing followed by locomotor training |
Primary outcome
Plasticity of Spinal Neuronal Networks - Homosynaptic Depression
Time frame: 4-6 months
Soleus H-reflexes following posterior tibial nerve stimulation with a 1-ms monophasic pulse were recorded with subjects seated and stimuli delivered every 1 s (1.0 Hz), 3 s (0.33 Hz), 5 s (0.2 Hz), 8 s (0.125 Hz), and 10s (0.1 Hz). Results for each interval vs 0.1 Hz shown.
Plasticity of Spinal Neuronal Networks - Presynaptic Inhibition
Time frame: 4-6 months
Presynaptic inhibition was assessed with a conditioning pulse train of 4 pulses with 9 ms duration, delivered to the CPN at the C-T intervals of 20, 60, or 100 ms. These C-T intervals were selected because the reflex inhibition produced at the intermediate C-T intervals is predominantly presynaptic. The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively. Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged. Results are listed for each C-T interval, pre- and post-intervention.
Plasticity of Spinal Neuronal Networks - Reciprocal Inhigition
Time frame: 4-6 months
To assess restoration of reciprocal Ia inhibition, soleus H-reflexes were recorded following common peroneal nerve (CPN) stimulation at short conditioning-test (C-T) intervals of 0, 1, 2, 3, and 4 ms. The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively. Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged. Results are listed for each C-T interval, pre- and post-intervention.
Plasticity of Corticospinal Networks
Time frame: 4-6 months
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. The tibialis anterior resting motor threshold (RMT) was established and corresponded to the lowest TMS maximal stimulator output that induced reproducible evoked potentials of at least ~50 µV in 4 out of 5 consecutive single TMS pulses. RMTs (percentage of maximal stimulator output) are shown pre- and post-intervention.
3 secondary outcomes
Ambulatory Function
Time frame: 4-6 months
Balance
Time frame: 4-6 months
Autonomic Function
Time frame: 4-6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29988534Cote MP, Murray LM, Knikou M. Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions. Front Physiol. 2018 Jun 25;9:784. doi: 10.3389/fphys.2018.00784. eCollection 2018.
- Background: PubMed 17551860Ellaway PH, Catley M, Davey NJ, Kuppuswamy A, Strutton P, Frankel HL, Jamous A, Savic G. Review of physiological motor outcome measures in spinal cord injury using transcranial magnetic stimulation and spinal reflexes. J Rehabil Res Dev. 2007;44(1):69-76. doi: 10.1682/jrrd.2005.08.0140.
- Background: PubMed 18677185Wirth B, van Hedel HJ, Curt A. Ankle paresis in incomplete spinal cord injury: relation to corticospinal conductivity and ambulatory capacity. J Clin Neurophysiol. 2008 Aug;25(4):210-7. doi: 10.1097/WNP.0b013e318183f4e3.
- Background: PubMed 25814508Cirillo J, Calabro FJ, Perez MA. Impaired Organization of Paired-Pulse TMS-Induced I-Waves After Human Spinal Cord Injury. Cereb Cortex. 2016 May;26(5):2167-77. doi: 10.1093/cercor/bhv048. Epub 2015 Mar 25.
- Background: PubMed 19320005Arvanian VL, Schnell L, Lou L, Golshani R, Hunanyan A, Ghosh A, Pearse DD, Robinson JK, Schwab ME, Fawcett JW, Mendell LM. Chronic spinal hemisection in rats induces a progressive decline in transmission in uninjured fibers to motoneurons. Exp Neurol. 2009 Apr;216(2):471-80. doi: 10.1016/j.expneurol.2009.01.004.
- Background: PubMed 17250567Nielsen JB, Crone C, Hultborn H. The spinal pathophysiology of spasticity--from a basic science point of view. Acta Physiol (Oxf). 2007 Feb;189(2):171-80. doi: 10.1111/j.1748-1716.2006.01652.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Knikou, PT, PhD principal investigator
Research Foundation of the City University of New York
Noam Y. Harel, MD, PhD principal investigator
Bronx Veterans Medical Research Foundation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standing transspinal stimulation followed by robotic gait training and Lying transspinal stimulation followed by robotic gait training in people with Spinal Cord Injuries and Paraplegia, Spinal, run by City University of New York at 2 sites 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 12 inclusion and 13 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: finished, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 18 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasticity of Spinal Neuronal Networks - Homosynaptic Depression (time frame: 4-6 months). The study lists 4 primary outcomes in all. 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 NCT04807764, which also lists 142 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 18 Aug 2026.