Spinal Cord InjuryPhase 1/2NCT07223710
Improving Walking After Spinal Cord Injury
A Phase 1/2 study testing Paired Associative Stimulation and Locomotor Training in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab at 1 site in United States.
Trial summary
Locomotor recovery is one of the most important goals of individuals with spinal cord injury (SCI). Ambulatory deficits severely impact daily functions resulting in lower quality of life for people living with paralysis due to SCI. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Paired Associative Stimulation and Locomotor Training
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2025to 30 Jul 2026
- Phase
- Phase 1/2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of traumatic or non-traumatic SCI ≥ 6 months
- International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) level at and above T10.
- American Spinal Injury Association AIS Grade C, or D
- Weakness in ankle dorsiflexors (LEMS<=3) with the ability to perform a small voluntary ankle dorsiflexion (as detected by presence of voluntary EMG activity in the tibialis anterior) with at least one leg.
- Ability to tolerate standing position.
- Ability to walk at a minimum speed of 0.1 mile/hour on a treadmill with less than 70% body weight support.
- Requires use of assistive devices (KAFO, AFO, cane, walker) or body weight support for ambulation.
- Ability to complete the 10-Meter Walk Test.
Who cannot join
- Preceding uncontrolled medical conditions including pulmonary, cardiovascular or orthopedic disease that interfere with physical performance.
- Intolerance to physical activity.
- Severe cognitive impairment that precludes the ability to participate in any of the study procedures or give verbal consent.
- Any illness or condition that based on the research team's assessment, will compromise with the patient's ability to comply with the protocol, patient safety, or the validity of the data collected during the study.
- History of stroke resulting in sensory motor deficits.
- Pregnant women.
Show all 10Show fewer
- Participation in a high-intensity locomotor training program in the last 6 months.
- Inability to detect somatosensory evoked potentials
- Metal implant in the head
- History of epilepsy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Shirley Ryan AbilityLab
Chicago, Illinois, 60611
Dalia De Santis, 312-238-7895, ddesantis@sralab.org
Dalia De Santis, PhD
About this study
Official title: Engaging Reticulospinal Inputs to Improve Walking Ability in Humans With Spinal Cord Injury
Locomotor recovery is one of the most important goals of individuals with spinal cord injury (SCI). Ambulatory deficits severely impact daily functions resulting in lower quality of life for people living with paralysis due to SCI. Although studies have shown that locomotor training improves locomotor function in people with chronic SCI, the benefits remain limited. Our overall hypothesis is that we can engage additional descending motor pathways, such as the reticulospinal tract (RST), to improve locomotor function in humans with chronic incomplete SCI.
In this study we propose to test the effects of a novel intervention that uses repeated paired loud auditory and electrical stimulation of muscle afferents combined with locomotor training on walking speed and voluntary muscle strength.
Read the detailed description
Individuals with chronic incomplete SCI will be randomly assigned to a group that will receive 10 sessions of a startle stimulus (a very brief, loud sound) and electrical stimulation combined with locomotor training or 10 sessions of a non-startle stimulus (a very brief, soft sound) combined with locomotor training.
- Conditions
- Spinal Cord Injury
- Being tested
- Paired Associative Stimulation, Locomotor Training, Sham stimulation
- Keywords
- auditory stimulation, peripheral stimulation, locomotion training, descending motor tracts
- 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.
Paired Associative StimulationDevice
Also called PAS
This new intervention consists of locomotor training in combination with paired low-intensity electrical stimulation and stimulation of the reticulospinal tract through loud sounds. Participants will receive auditory stimulation (LAS, 110dB, 500Hz, 50ms) through headphones and electrical stimulation through a pair of electrodes with 2cm inter-electrode distance positioned on the motor point over the quadriceps and the tibialis anterior muscles bilaterally. The motor point will be identified as the position of the electrodes that elicits a small visible muscle twitch or muscle contraction upon palpation over the tendon with the minimum stimulation intensity. Stimuli will be delivered with a pulse duration of 200 microseconds and will be timed to arrive at the level of the brainstem ~7ms before auditory signals.
Locomotor TrainingBehavioural
Participants will walk on a treadmill with body-weight support (ZeroG, Aretech) in the range 0-70% as needed to prevent excessive knee flexion during stance phase or toe dragging during swing phase (Finch et al. 1991). Each session will last approximately 60-min and the duration of the treadmill training will be timed to be 30 min. Subjects will be encouraged to walk at a self-selected speed at or above 0.1m/s. Speed and body-weight support will be adjusted to achieve a perceived exertion score of 4-5 (Moderate) in the Borg scale (Borg 1982). Subjects will be allowed to rest as needed during the training sessions.
Sham stimulationDevice
Participants will receive brief low-intensity auditory clicks (80dB, 500Hz, 50ms) through headphones and electrical stimulation through a pair of electrodes with 2cm inter-electrode distance positioned on the motor point over the quadriceps and the tibialis anterior muscles bilaterally. The motor point will be identified as the position of the electrodes that elicits a small visible muscle twitch or muscle contraction upon palpation over the tendon with the minimum stimulation intensity. Stimuli will be delivered with a pulse duration of 200 microseconds and will be timed to arrive at the level of the brainstem ~7ms before auditory signals.
| Study group | Role | What they receive |
|---|---|---|
| Locomotor training + PAS | Experimental | This intervention uses repeated paired loud auditory and electrical stimulation of muscle afferents combined with locomotor training.
Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief loud auditory stimuli through headphones and short electrical pulses through of electrodes positioned on two points in the leg Receives: Device: Paired Associative Stimulation; Behavioral: Locomotor Training |
| Locomotor training + SHAM | Sham comparator | This sham intervention uses repeated paired soft auditory clicks and electrical stimulation of muscle afferents combined with locomotor training.
Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief auditory clicks through headphones and short electrical pulses through a pair of electrodes positioned on two points in the leg. Receives: Behavioral: Locomotor Training; Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
10-meter walk test (10MWT)
This standardized test assesses walking speed in meters per second over a short duration.
Measured: baseline and day 12
Secondary outcomes (6)
Motor Evoked Potentials conditioned with Startle (MEP-LAS)
Motor Evoked Potentials (MEPs) will be recorded from multiple leg muscles following transcranial magnetic stimulation over the leg representation of the primary motor cortex and electrical stimulation over the thoracic spine. Loud auditory Stimuli (LAS, 110dB, 500Hz, 50ms) will be delivered 50ms before magnetic stimulation to test for cortical effects of the intervention and 80ms before the electrical stimulation to test for subcortical effects of the intervention. Stimulation intensity will be adjusted to obtain unconditioned MEPs of ~50% of the maximum MEP for each muscle.
Measured: Baseline and day 12
Maximum Voluntary Contraction (MVC)
This will be measured on the electromyographic signal recorded during maximal isometric contractions. Participants will perform three maximal contractions against resistance into knee flexion and extension, dorsiflexion, and plantarflexion. Electromyographic activity will be monitored using surface electrodes placed on the belly of the quadriceps femoris, hamstrings, tibialis anterior, and soleus muscles bilaterally. The MVC will be quantified as the maximum value of the average over 1s of activity in each of the repetitions.
Measured: Baseline and day 12
Maximal motor response (M-max)
M-max will be elicited in the quadriceps femoris, tibialis anterior, soleus and foot muscles by applying percutaneous electrical stimulation over the femoral, common peroneal and the tibial and the medial plantar nerve, respectively using 200μs rectangular electrical stimulus. The intensity of stimulation will be increased progressively until M-max is reached.
Measured: Baseline and day 12
StartReact response
Participants will be asked to observe a light-emitting diode (LED) located ~1 m in front of the participants' head and will be wearing headphones. When the LED will illuminate (20 ms), individuals will be asked to perform an isometric knee flexion/extension and/or ankle dorsi/plantarflexion as fast as possible. Reaction times will be evaluated following a visual cue either alone (20 trials) or paired with a non-startling (80dB, 500Hz, 50ms, 20 trials) or a startling (110dB, 500Hz, 50ms, 20 trials) auditory cue. Stimuli will be delivered every 5s in a randomized order. Target muscles will be quadriceps femoris, hamstrings, tibialis anterior, and soleus muscles of the weaker leg. The StartReact response will be computed as the difference between the reaction times during a non-startling and startling auditory cue
Measured: Baseline and day 12
Spasticity
We will use the Modified Ashworth scale (six-point ordinal scale, 0-4) to measure resistance encountered during manual passive muscle stretching.
Measured: Baseline and day 12
SCI-QOL
Is a battery of questionnaires evaluating the quality of life. Will be used to measure the participant-related following aspects: (a) Ambulation: This questionnaire will ask the participant about their ability to do thing like walk, run and jump. (b) Basic Mobility: This questionnaire will ask the participant about their ability to perform their daily routine. (c) Fine Motor: This questionnaire will ask the participant about their ability to pick up small objects. (d) Manual and Power Wheelchair Mobility: This questionnaire ask the participant about their ability using a wheelchair. (e) Self-Care: This questionnaire will ask the participant about their ability to do activities of daily living such as getting dressed, bathing, and eating.
Measured: Baseline and day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2025
- Study start15 Nov 2025 (estimated)
- Primary completion30 Mar 2026 (estimated)
- Study completion30 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuryStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shirley Ryan AbilityLab
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Dalia DeSantis, Shirley Ryan AbilityLab
- Investigators
- Dalia De Santis, PhD, Principal investigator, Shirley Ryan AbilityLab
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07223710
- Sponsor's protocol ID
- STU00222004
- Other IDs
- R03HD114768-01
- Status last verified
- Oct 2025
- First submitted
- 27 Oct 2025
- Last updated
- 3 Nov 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data related to Demographics, clinical outcomes and instrumental data will shared through the NICHD Data ad Specimens Hub (DASH).
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Engaging Reticulospinal Inputs to Improve Walking Ability in Humans With Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT07223710
- Acronym / sponsor ID
- STU00222004
- Conditions
- Spinal Cord Injury
- Keywords
- auditory stimulation, peripheral stimulation, locomotion training, descending motor tracts
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shirley Ryan AbilityLabUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 15 Nov 2025 (estimated)
- Primary completion
- 30 Mar 2026 (estimated)
- Study completion
- 30 Jul 2026 (estimated)
- First posted
- 3 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Locomotor recovery is one of the most important goals of individuals with spinal cord injury (SCI). Ambulatory deficits severely impact daily functions resulting in lower quality of life for people living with paralysis due to SCI. Although studies have shown that locomotor training improves locomotor function in people with chronic SCI, the benefits remain limited. Our overall hypothesis is that we can engage additional descending motor pathways, such as the reticulospinal tract (RST), to improve locomotor function in humans with chronic incomplete SCI.
In this study we propose to test the effects of a novel intervention that uses repeated paired loud auditory and electrical stimulation of muscle afferents combined with locomotor training on walking speed and voluntary muscle strength.
Detailed description
Individuals with chronic incomplete SCI will be randomly assigned to a group that will receive 10 sessions of a startle stimulus (a very brief, loud sound) and electrical stimulation combined with locomotor training or 10 sessions of a non-startle stimulus (a very brief, soft sound) combined with locomotor training.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Locomotor training + PAS | Experimental | Device: Paired Associative Stimulation, Behavioral: Locomotor TrainingThis intervention uses repeated paired loud auditory and electrical stimulation of muscle afferents combined with locomotor training. Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief loud auditory stimuli through headphones and short electrical pulses through of electrodes positioned on two points in the leg |
| Locomotor training + SHAM | Sham comparator | Behavioral: Locomotor Training, Device: Sham stimulationThis sham intervention uses repeated paired soft auditory clicks and electrical stimulation of muscle afferents combined with locomotor training. Participants will exercise walking on a treadmill with body weight support as needed for 30 minutes a day at a moderate intensity. While walking, participants will receive brief auditory clicks through headphones and short electrical pulses through a pair of electrodes positioned on two points in the leg. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- History of traumatic or non-traumatic SCI ≥ 6 months
- International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) level at and above T10.
- American Spinal Injury Association AIS Grade C, or D
- Weakness in ankle dorsiflexors (LEMS<=3) with the ability to perform a small voluntary ankle dorsiflexion (as detected by presence of voluntary EMG activity in the tibialis anterior) with at least one leg.
- Ability to tolerate standing position.
Key exclusion criteria (10 listed)
- Preceding uncontrolled medical conditions including pulmonary, cardiovascular or orthopedic disease that interfere with physical performance.
- Intolerance to physical activity.
- Severe cognitive impairment that precludes the ability to participate in any of the study procedures or give verbal consent.
- Any illness or condition that based on the research team's assessment, will compromise with the patient's ability to comply with the protocol, patient safety, or the validity of the data collected during the study.
- History of stroke resulting in sensory motor deficits.
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 |
|---|---|---|
| Paired Associative StimulationAlso: PASThis new intervention consists of locomotor training in combination with paired low-intensity electrical stimulation and stimulation of the reticulospinal tract through loud sounds. Participants will receive auditory stimulation (LAS, 110dB, 500Hz, 50ms) through headphones and electrical stimulation through a pair of electrodes with 2cm inter-electrode distance positioned on the motor point over the quadriceps and the tibialis anterior muscles bilaterally. The motor point will be identified as the position of the electrodes that elicits a small visible muscle twitch or muscle contraction upon palpation over the tendon with the minimum stimulation intensity. Stimuli will be delivered with a pulse duration of 200 microseconds and will be timed to arrive at the level of the brainstem ~7ms before auditory signals. | Device | Locomotor training + PAS |
| Locomotor TrainingParticipants will walk on a treadmill with body-weight support (ZeroG, Aretech) in the range 0-70% as needed to prevent excessive knee flexion during stance phase or toe dragging during swing phase (Finch et al. 1991). Each session will last approximately 60-min and the duration of the treadmill training will be timed to be 30 min. Subjects will be encouraged to walk at a self-selected speed at or above 0.1m/s. Speed and body-weight support will be adjusted to achieve a perceived exertion score of 4-5 (Moderate) in the Borg scale (Borg 1982). Subjects will be allowed to rest as needed during the training sessions. | Behavioural | Locomotor training + PAS, Locomotor training + SHAM |
| Sham stimulationParticipants will receive brief low-intensity auditory clicks (80dB, 500Hz, 50ms) through headphones and electrical stimulation through a pair of electrodes with 2cm inter-electrode distance positioned on the motor point over the quadriceps and the tibialis anterior muscles bilaterally. The motor point will be identified as the position of the electrodes that elicits a small visible muscle twitch or muscle contraction upon palpation over the tendon with the minimum stimulation intensity. Stimuli will be delivered with a pulse duration of 200 microseconds and will be timed to arrive at the level of the brainstem ~7ms before auditory signals. | Device | Locomotor training + SHAM |
Primary outcome
10-meter walk test (10MWT)
Time frame: baseline and day 12
This standardized test assesses walking speed in meters per second over a short duration.
6 secondary outcomes
Motor Evoked Potentials conditioned with Startle (MEP-LAS)
Time frame: Baseline and day 12
Maximum Voluntary Contraction (MVC)
Time frame: Baseline and day 12
Maximal motor response (M-max)
Time frame: Baseline and day 12
StartReact response
Time frame: Baseline and day 12
Spasticity
Time frame: Baseline and day 12
SCI-QOL
Time frame: Baseline and day 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2025.
- Individual participant dataSharing planned: Yes. De-identified data related to Demographics, clinical outcomes and instrumental data will shared through the NICHD Data ad Specimens Hub (DASH).
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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.
Dalia De Santis, PhD principal investigator
Shirley Ryan AbilityLab
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Paired Associative Stimulation and Locomotor Training in people with Spinal Cord Injury, run by Shirley Ryan AbilityLab 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 8 inclusion and 10 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: opening soon, as of the sponsor's last update on 3 Nov 2025. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Dalia De Santis (312-238-7895, ddesantis@sralab.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
10-meter walk test (10MWT) (time frame: baseline and day 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Nov 2025; AzTrials last refreshed its copy on 30 Oct 2026.