An interventional study of Single-Electrode Tonic tSCS and Multi-Electrode Spatiotemporal tSCS in Spinal Cord Injuries (SCI), sponsored by University of Sao Paulo General Hospital. Enrolling by invitation at 1 site in Brazil. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-26.
Sponsored by University of Sao Paulo General Hospital · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to investigate whether personalized multi-electrode transcutaneous spinal cord stimulation (tSCS), guided by machine learning (ML) and combined with gait training, can improve walking function in people with spinal cord injury or stroke compared with single-electrode tonic stimulation combined with the same training.
tSCS is a non-invasive technique that delivers electrical pulses through electrodes placed on the skin over the spine to modulate spinal neural circuits, facilitate the recruitment of lower-limb muscles, and support the recovery of voluntary movements. Conventional tSCS typically uses a single stimulation electrode, which may limit selective recruitment of different muscle groups. This study investigates a personalized multi-electrode approach to selectively recruit specific lower-limb muscle groups and deliver stimulation at appropriate phases of the gait cycle, with the aim of improving walking function.
The main questions this study aims to answer are:
The study includes 24 participants (14 with spinal cord injury and 10 with stroke) and consists of two stages.
Stage 1 - Characterization of tSCS Selectivity and Stimulation Optimization
All participants complete two experimental sessions while lying down. Researchers compare muscle responses to stimulation at a central electrode and at multiple spinal electrode locations. Electrical responses in the leg muscles are recorded using surface electromyography (EMG), and spinal reflexes are assessed using paired electrical pulses.
By systematically testing electrode positions and stimulation intensities, researchers build a map of which leg muscles respond to each setting (stimulation landscape). They assess the selective recruitment of different muscle groups, compare stimulation locations, and examine differences between participants and across the two sessions. They also test whether ML-based optimization can find similarly selective settings more efficiently than the complete mapping procedure.
Stage 2 - tSCS Combined With Gait Training
Participants are randomly assigned to one of two groups: single-electrode or multi-electrode tSCS, both combined with gait training. During spinal cord injury recruitment, the randomization procedure was adapted to better balance participants with different baseline walking abilities across groups.
Before each training session, participants lie down for an individualized calibration. An ML-based optimization method uses recorded muscle responses to select electrode positions and stimulation intensities for the subsequent walking session.
During walking, the single-electrode group receives continuous stimulation through one selected electrode. In the multi-electrode group, stimulation is delivered through electrodes selected to preferentially recruit different target muscle groups. A predefined walking-cycle model determines when stimulation should be delivered, based on gait phases detected in real time by wearable movement sensors.
Both groups complete 20 supervised training sessions over four weeks, including 30 minutes of treadmill walking per session. Walking speed is selected according to each participant's comfort and ability, with therapist adjustments, body-weight support, and physical assistance as needed.
Clinical and functional assessments are conducted before the intervention (T0), after the 20 sessions (T1), and at a 30-day follow-up (T2). They examine walking performance, muscle strength, spasticity, balance, and mobility. Additional measurements assess muscle activation, brain activity, and biological markers associated with neuroplasticity. The follow-up assesses whether changes are maintained after training.
Background and Rationale
Transcutaneous spinal cord stimulation (tSCS) is a non-invasive neuromodulation approach that modulates spinal sensorimotor circuits through the recruitment of afferent fibers. When combined with rehabilitation, tSCS may facilitate voluntary motor control and functional recovery in individuals with spinal cord injury (SCI) or stroke.
Conventional tSCS commonly applies tonic stimulation through a single electrode, which may limit the ability to preferentially recruit specific lower-limb muscle groups. This study investigates a personalized multi-electrode approach combining machine-learning (ML)-based optimization of stimulation settings with a predefined feedforward strategy that coordinates stimulation with the walking cycle. Stimulation configurations are selected according to individual muscle responses during calibration and then activated according to gait phases detected during walking.
The study has three objectives: (1) to assess the selectivity of tSCS and characterize the spatial distribution and between-participant and between-session variability of muscle recruitment; (2) to assess whether ML-based optimization identifies selective stimulation configurations more efficiently than systematic mapping of muscle responses; and (3) to compare changes in walking function following multi-electrode versus single-electrode tonic tSCS, both combined with gait training.
Study Design
This is a prospective, controlled, randomized, parallel-group interventional study involving 24 participants, including 14 with SCI and 10 with stroke. The protocol includes two sequential stages: electrophysiological characterization and stimulation optimization, followed by a gait-training intervention.
All participants undergo the first stage. For the second stage, participants are assigned to one of two intervention groups: single-electrode or multi-electrode tSCS, both combined with gait training.
The initial allocation procedure used simple randomization. During SCI recruitment, stratified randomization based on baseline walking ability (ambulatory or non-ambulatory) was introduced to improve balance between the intervention groups. The SCI sample size was increased to 14 participants. Each participant receives only one of the two interventions throughout the training program.
Stage 1 - Characterization of tSCS Selectivity and ML-Based Optimization
All participants complete two sessions in a supine position to examine muscle recruitment selectivity and the reproducibility of responses across days.
Stimulation is tested using a central spinal electrode and multiple electrode locations over the thoracolumbar region. Posterior root-muscle (PRM) reflexes are assessed with paired-pulse stimulation, and evoked responses are recorded bilaterally by surface electromyography (EMG).
Systematic testing of electrode positions and stimulation intensities is used to construct individual stimulation landscapes. These maps describe the distribution of evoked lower-limb muscle responses across stimulation settings, with particular attention to four target groups: left proximal, right proximal, left distal, and right distal muscles. They are used to compare recruitment selectivity between stimulation configurations and to examine variability between participants and between the two sessions.
An ML-based optimization method is evaluated for identifying settings that preferentially recruit target muscle groups. Its results are compared with the comprehensive stimulation landscapes, focusing on achieved selectivity, the number of stimulation tests needed, and the time required to identify suitable configurations.
Stage 2 - tSCS Combined With Gait Training
Participants complete 20 supervised gait-training sessions over four weeks (five sessions per week). Each session includes a supine calibration procedure before gait training. Muscle responses recorded during electrical stimulation are used by the ML-based method to select individualized electrode positions and stimulation intensities. This repeated calibration allows settings to be adapted to day-to-day differences in responses.
Single-Electrode tSCS
For the single-electrode intervention, calibration identifies a stimulation electrode and intensity intended to recruit lower-limb muscles broadly. During gait training, continuous tonic stimulation is delivered through the selected electrode.
Multi-Electrode tSCS
For the multi-electrode intervention, calibration identifies configurations that preferentially recruit different target muscle groups. A predefined feedforward gait model specifies when each configuration should be activated during the walking cycle. Wearable inertial measurement units (IMUs) detect gait phases in real time, and the stimulation system uses this information to deliver the previously selected stimulation patterns at the corresponding phases. Optimization of stimulation settings is performed before, rather than during, walking.
Gait Training Procedure
Both groups receive 30 minutes of treadmill-based gait training per session with a body-weight support system. Participants walk at a comfortable, self-selected speed, with therapist adjustments when necessary. Body-weight support and additional physical assistance are adapted to each participant's functional abilities and safety needs.
Clinical, Biomechanical, and Neurophysiological Assessments
Clinical and functional evaluations take place before the intervention (T0), after completion of the 20 training sessions (T1), and at a 30-day follow-up (T2). The main intervention comparisons focus on changes from T0 to T1; T2 is used to examine the maintenance of changes after training.
Functional assessments cover walking performance and independence, mobility, balance, lower-limb strength, and spasticity. Measures include the 10-Meter Walk Test (10MWT), Timed Up and Go (TUG), Berg Balance Scale, Medical Research Council muscle strength scale, and Modified Ashworth Scale, together with population-specific assessments such as the Walking Index for Spinal Cord Injury II (WISCI II) and the Fugl-Meyer Assessment of the Lower Extremity. Assessments are performed according to each participant's functional abilities.
Surface EMG and wearable sensors assess muscle activity and gait characteristics. Three-dimensional motion capture is used when feasible according to the participant's walking ability. Additional investigations include electroencephalography (EEG) for cortical activity, functional near-infrared spectroscopy (fNIRS) for cortical hemodynamic responses, and blood-based analyses of brain-derived neurotrophic factor (BDNF) and genetic variants related to neuroplasticity. The timing of these measurements follows the schedule for each assessment modality.
The study aims to provide evidence on muscle recruitment selectivity, the efficiency of ML-guided calibration, and the functional and physiological effects of personalized multi-electrode tSCS for gait rehabilitation in SCI and stroke.
1,991 studies on the registry are indexed under Spinal Cord Injuries; 516 are open to participants now.
This study's planned enrollment of 24 is close to the median of 24 across 1,594 interventional studies indexed under Spinal Cord Injuries.
Browse Spinal Cord Injuries studies →University of Sao Paulo General Hospital is the lead sponsor of 609 studies on the registry; 98 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
General Criteria:
Spinal Cord Injury:
Stroke:
Exclusion Criteria:
Participants receive single-electrode tonic transcutaneous spinal cord stimulation (tSCS) combined with treadmill-based gait training. Before each training session, individualized stimulation calibration is performed in a supine position using muscle responses recorded by surface electromyography (EMG). A single electrode and stimulation intensity are selected to promote broad recruitment of lower-limb muscle groups rather than selective activation of individual muscle groups. During walking, tonic stimulation is delivered continuously through the selected electrode. Participants complete 20 supervised training sessions over four weeks, including 30 minutes of treadmill walking per session, with individualized body-weight support and physical assistance as needed.
Device: Single-Electrode Tonic tSCS
Participants receive personalized multi-electrode transcutaneous spinal cord stimulation (tSCS) combined with treadmill-based gait training. Before each training session, machine-learning-based optimization is performed in a supine position using muscle responses recorded by surface electromyography (EMG). Electrode configurations and stimulation intensities are individually selected to preferentially recruit specific lower-limb muscle groups, including proximal and distal muscles on both sides. During walking, wearable inertial sensors detect gait phases in real time, allowing the previously selected electrode configurations to be activated at the corresponding phases according to a predefined gait model. Participants complete 20 supervised training sessions over four weeks, including 30 minutes of treadmill walking per session, with individualized body-weight support and physical assistance as needed.
Device: Multi-Electrode Spatiotemporal tSCS
Non-invasive transcutaneous spinal cord stimulation delivered through a single active spinal electrode. Before each gait-training session, individualized calibration is performed to select an electrode position and stimulation intensity intended to promote broad recruitment of lower-limb muscles, based on evoked muscle responses recorded by surface EMG. During treadmill walking, continuous tonic stimulation is delivered through the selected electrode, without phase-specific modulation.
Also known as: tSCS
Participants receive personalized multi-electrode transcutaneous spinal cord stimulation (tSCS) combined with treadmill-based gait training. Before each training session, machine-learning-based optimization is performed in a supine position using muscle responses recorded by surface electromyography (EMG). Electrode configurations and stimulation intensities are individually selected to preferentially recruit specific lower-limb muscle groups, including proximal and distal muscles on both sides. During walking, wearable inertial sensors detect gait phases in real time, allowing the previously selected electrode configurations to be activated at the corresponding phases according to a predefined gait model. Participants complete 20 supervised training sessions over four weeks, including 30 minutes of treadmill walking per session, with individualized body-weight support and physical assistance as needed.
Also known as: spatio-temporal tSCS
Change in Walking Speed Assessed by the 10-Meter Walk Test (10MWT)
Comfortable overground walking speed will be assessed using the 10-Meter Walk Test (10MWT) and expressed in meters per second (m/s). Assistive devices and orthoses will be permitted and documented. Participants unable to complete the test due to insufficient walking ability will be assigned a value of 0 m/s for the primary analysis. This value represents inability to perform the test rather than a measured walking speed. The primary outcome will be the change in walking speed from baseline to completion of the intervention, compared between the single-electrode and multi-electrode tSCS groups. Assessment procedures will be standardized across visits.
Time frame: Baseline (T0) and after 4 weeks of intervention (T1)
Change in Walking Ability Assessed by the Walking Index for Spinal Cord Injury II (WISCI II)
Walking ability in participants with spinal cord injury will be assessed using the Walking Index for Spinal Cord Injury II (WISCI II). The scale ranges from 0 to 20 and classifies walking performance according to the need for physical assistance, assistive devices, and orthoses. Higher scores indicate greater walking ability. Changes in WISCI II scores will be evaluated across assessment visits.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Lower-Limb Motor Function Assessed by the Fugl-Meyer Assessment (FMA-LE)
Lower-limb motor function in participants with stroke will be assessed using the lower-extremity motor subscale of the Fugl-Meyer Assessment (FMA-LE). Motor scores range from 0 to 34, with higher scores indicating better motor function. Changes in FMA-LE motor scores will be evaluated across assessment visits.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Lower-Limb Muscle Strength Assessed by the Medical Research Council (MRC) Scale
Lower-limb muscle strength will be assessed using the Medical Research Council (MRC) scale. Individual muscle groups will be graded from 0 (no visible muscle contraction) to 5 (normal muscle strength). Changes in muscle strength will be evaluated in participants with spinal cord injury and stroke. Scores for the assessed muscle groups will be reported separately rather than combined into an unspecified composite score.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Lower-Limb Spasticity Assessed by the Modified Ashworth Scale (MAS)
Resistance to passive movement in lower-limb muscle groups will be assessed using the Modified Ashworth Scale (MAS). The scale includes the ordinal grades 0, 1, 1+, 2, 3, and 4, with higher grades indicating greater resistance to passive movement. Changes in MAS grades will be evaluated for the assessed muscle groups without combining them into an unspecified total score-
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Balance Assessed by the Berg Balance Scale (BBS)
Balance performance will be evaluated using the Berg Balance Scale (BBS), which includes 14 tasks assessing static and dynamic balance. Total scores range from 0 to 56, with higher scores indicating better balance performance. Changes in total BBS scores will be evaluated across assessment visits.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Functional Mobility Assessed by the Timed Up and Go Test (TUG)
Functional mobility will be assessed using the Timed Up and Go (TUG) test. The test measures the time, in seconds, required to stand from a chair, walk 3 meters, turn around, return to the chair, and sit down. Lower completion times indicate better functional mobility. Assistive devices may be used as needed and will be documented. Participants unable to complete the test will be recorded as unable to perform the assessment rather than assigned an arbitrary completion time.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Walking Speed at 30-Day Follow-Up Assessed by the 10MWT
Comfortable overground walking speed will be assessed using the 10-Meter Walk Test (10MWT) and expressed in meters per second (m/s). The outcome will be the change in walking speed from baseline to the 30-day follow-up after completion of the intervention. The same assessment procedures, documentation of assistive devices, and scoring rules defined for the primary outcome will be applied.
Time frame: Baseline (T0) and 30-day follow-up after completion of the intervention (T2)
Gait-Phase-Dependent Muscle Activation Assessed by the Phase Selectivity Index (PSI)
Gait-phase-dependent muscle activation will be assessed using surface electromyography (EMG) recorded bilaterally from lower-limb muscles. The Phase Selectivity Index (PSI) will be calculated from the root mean square (RMS) EMG amplitude during the target gait phase relative to the non-target phase. PSI ranges from -100% to 100%, with higher values indicating greater preferential activation during the intended gait phase. Values will be evaluated for individual recorded muscles to characterize the temporal coordination of muscle activation during walking.
Time frame: During the first and twentieth gait-training sessions (approximately 4 weeks apart)
Change in Spatial Gait Parameters Assessed by Instrumented Gait Analysis
Spatial gait characteristics will be evaluated using wearable inertial measurement units (IMUs) and/or three-dimensional motion capture. Measures include step length, stride length, and step width, all expressed in centimeters (cm). These parameters characterize the spatial dimensions of gait and will be examined as separate component measures, without calculation of a composite score. Bilateral measurements will be retained when available.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Walking Speed Assessed by Instrumented Gait Analysis
Walking speed will be evaluated during instrumented gait analysis using wearable inertial measurement units (IMUs) and/or three-dimensional motion capture. Speed will be expressed in centimeters per second (cm/s). This laboratory-based measure characterizes walking performance under the standardized gait assessment conditions and will be analyzed separately from the overground 10-Meter Walk Test.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Gait Cadence Assessed by Instrumented Gait Analysis
Gait cadence will be evaluated using wearable inertial measurement units (IMUs) and/or three-dimensional motion capture. Cadence will be expressed in steps per minute and represents the number of steps performed per unit of time. Changes in gait cadence will be used to characterize temporal aspects of walking performance.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Temporal Gait Phase Parameters Assessed by Instrumented Gait Analysis
Temporal gait characteristics will be assessed using wearable inertial measurement units (IMUs) and/or three-dimensional motion capture. Measures include stance phase duration, swing phase duration, initial double-support duration, and single-support duration. Each parameter will be expressed as a percentage of the gait cycle (%). These measures characterize the distribution of time across gait phases and will be evaluated as separate components rather than combined into a composite score.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Resting-State EEG Spectral Power
Resting-state cortical activity will be assessed using electroencephalography (EEG) under eyes-open and eyes-closed conditions. Power spectral density will be calculated in predefined frequency bands (delta, theta, alpha, beta, and gamma) to quantify cortical oscillatory activity. Spectral power will be assessed separately by frequency band and recording condition, with comparisons of cortical activity across assessment visits.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Cortical Hemodynamic Response Assessed by fNIRS
Task-related cortical hemodynamic activity during gait training will be assessed using functional near-infrared spectroscopy (fNIRS). Changes in oxygenated hemoglobin (HbO) concentration will be estimated using a general linear model (GLM) in predefined cortical regions of interest involved in motor control. The HbO hemodynamic response will be used to assess changes in cortical activation associated with gait training.
Time frame: During the first and twentieth gait-training sessions (approximately 4 weeks apart)
Change in Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration
Serum brain-derived neurotrophic factor (BDNF) concentration will be quantified from peripheral blood samples using an immunoassay. Concentrations will be reported using the laboratory assay's specified units. Changes in serum BDNF concentration will be evaluated across assessment visits and compared between intervention groups as a circulating biomarker potentially associated with neuroplasticity.
Time frame: Baseline (T0), after 4 weeks of intervention (T1), and 30-day follow-up (T2)
Change in Body-Weight Support During Treadmill Gait Training
The amount of body-weight support provided during treadmill gait training will be recorded as a percentage of the participant's body weight (%). Lower percentages indicate reduced reliance on external body-weight support. Changes in the level of support used during training will be evaluated to characterize progression in weight-bearing capacity and walking performance.
Time frame: During the 20 gait-training sessions over 4 weeks
Change in Treadmill Walking Speed During Gait Training
Treadmill walking speed will be recorded during supervised gait-training sessions. Speed will be expressed in kilometers per hour (km/h) and adjusted according to each participant's walking ability and tolerance. Changes in treadmill walking speed will be evaluated to characterize progression in training performance across the intervention period.
Time frame: During the 20 gait-training sessions over 4 weeks
Plan to share: No — Individual participant data (IPD) will not be shared publicly due to the sensitive nature of the clinical and neurophysiological data collected from participants with spinal cord injury and stroke, as well as the potential risk of participant re-identification given the relatively small study population. Study findings will be disseminated through scientific publications and presentations using aggregated, non-identifiable data.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
No contact was published for this record. The registry link below has the sponsor’s details.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Sao Paulo General Hospital →