Multisite Transspinal Stimulation for Augmenting Recovery in Spinal Cord Injury

NCT07204184 | Recruiting DMC FDA Device

• 1 other identifier: C41217GM
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

A well-established rehabilitation strategy for improvements of standing and walking ability in persons with spinal cord injury (SCI) is step training on a motorized treadmill with body weight support. A promising intervention is stimulation of the spinal cord through the skin (transspinal). No single intervention is likely to significantly improve long-term function after SCI on its own. Rather, combinatorial treatments that work synergistically and can be used at different clinical settings is the answer to target recovery in people with SCI. The objective of this clinical trial is to develop a non-invasive combinatorial intervention that can be used worldwide in different clinical settings. The investigators will use cervical and lumbosacral transspinal stimulation to augment the benefits of locomotor training and affect vital body functions after SCI. The investigators will deliver non-invasive cervical and lumbosacral transspinal stimulation alone or with step training to improve upright posture, walking, bladder, sex, and bowel function in persons with incomplete SCI. The noninvasive nature of the intervention holds minimal risk that outweighs the benefits.

Conditions

Spinal Cord Injuries (Complete and Incomplete)

Keywords

transspinal stimulation; robotic gait training; locomotor training; non-invasive; multi-modal rehabilitation; clinical biomarkers; neurophysiological biomarkers; sensorimotor recovery

Outcome Measures

Primary Outcomes (7)

• Soleus H-reflex recruitment curve

  Investigators will deliver single pulses of 1 ms duration every 5 seconds at increasing intensities to the posterior tibial nerve behind the knee to assemble the soleus H-reflex recruitment curve. At least 50 responses will be recorded. From the recruitment curve, the investigators will estimate changes in the slope and stimulation intensities for reflex threshold.

  Before and 1 day after all intervention sessions are completed.

• Soleus H-reflex rate-dependent depression

  Soleus H-reflexes following posterior tibial nerve of the right leg behind the knee with a 1-ms pulse randomly at 1, 3, 5, 8, and 10 s inter-pulse intervals will be recorded. At each inter-pulse interval, 15 responses will be recorded. Stimulation will be delivered via a ball shape electrode and responses will be recorded from leg muscles with surface electrodes. The smaller the soleus H-reflex amplitude when evoked every 1 second the larger the spinal inhibition. Recovery of spinal inhibition will be considered when the soleus H-reflex depression at 1 second is statistically significant different before and after the intervention.

  Before and 1 day after all intervention sessions are completed.

• Soleus H-reflex phase-dependent modulation during stepping

  Each participant will step with the assistance of the Lokomat, and the investigators will record soleus H-reflexes randomly across 16 equal time bins into which each step cycle is divided. The posterior tibial nerve behind the knee will be stimulated at motor threshold. Stimulations will be triggered based on the foot switch signal. Under physiological conditions, the soleus H-reflex during walking largely is facilitated during the stance phase and inhibited during the swing phase. Recovery of spinal locomotor circuits will be based on the amplitude of the soleus H-reflex during the stance and swing phases of gait, and how much is facilitated and inhibited during the stance and swing phases after intervention compared to before intervention for each participant.

  Before and 1 day after all intervention sessions are completed.

• Leg transspinal evoked potentials recruitment curves

  The investigators will deliver single 1 ms pulses every 5 seconds at increasing intensities with a surface electrode to the low back to assemble the recruitment curves of transspinal evoked potentials recorded from leg muscles with surface electrodes. Participants will lay on their back on a treatment table. From the recruitment curve, the slope and excitation threshold will be established and the intervention will be considered effective when statistical significant differences on their amplitude between before and after values is established.

  Before and 1 day after all intervention sessions are completed.

• Flexor carpus radialis H-reflex recruitment curve

  The investigators will stimulate the median nerve with a bipolar surface electrode at the elbow with single 1-ms pulses at increasing intensities every 5 seconds while participants are seated. At least 50 responses will be recorded. From the recruitment curve, the slope and excitation threshold will be established. The intervention will be considered effective when statistical significant differences between before and after values is found.

  Before and 2 days after all intervention sessions are completed.

• Flexor carpus radialis H-reflex rate dependent depression

  Flexor carpus radialis H-reflexes following median nerve stimulation with a surface bipolar electrode of the right arm at the elbow with a 1-ms pulse will be recorded randomly at 1, 3, 5, 8, and 10 s inter-pulse intervals. At each inter-pulse interval, 15 responses will be recorded. Responses will be recorded from arm muscles with surface electrodes. Under physiological conditions, the reflex is smaller when evoked every 1 second compared to that evoked every 10 seconds. Recovery of spinal inhibition will be considered when a smaller reflex is evoked every 1 second after the intervention compared to that observed before intervention.

  Before and 2 days after all intervention sessions are completed.

• Arm transspinal evoked potentials recruitment curves

  The investigators will deliver single 1 ms pulses every 5 seconds at increasing intensities to the back of the neck with a surface electrode to assemble the recruitment curves of transspinal evoked potentials recorded from arm muscles with surface electrodes. Participants will lay on their back on a treatment table. From the recruitment curve, the slope and excitation threshold will be established and the intervention will be considered effective when statistical significant differences between before and after intervention is established.

  Before and 2 days after all intervention sessions are completed.

Secondary Outcomes (6)

• 2-Minute Walk Test

  Before and 1-day after all intervention sessions are completed.

• 10-Meter Walk Test

  Before and 1-day after all intervention sessions are completed.

• Sexual function

  Before and 1-day after completion of all intervention sessions.

• Bladder function

  Before and 1-day after completion of all intervention sessions.

• Bowel function

  Before and 1-day after all intervention sessions are completed.

Study Arms (2)

Multisite transspinal stimulation at rest

ACTIVE COMPARATOR

Cervical and lumbosacral non-invasive transspinal tonic stimulation will be delivered at 30 Hz frequency (charge-balanced, symmetric, biphasic rectangular pulses of a 1-ms width per phase) at paresthesia levels or higher depending on each participant's comfort level while participants rest lying on the back. A total of 20 sessions (weekdays excluding weekends and holidays), each for 1 hour, will be administered.

Device: Multisite transspinal stimulation at rest

Multisite transspinal stimulation during robotic gait training

ACTIVE COMPARATOR

The investigators will deliver cervical and lumbosacral non-invasive transspinal tonic stimulation at 30 Hz frequency (charge-balanced, symmetric, biphasic rectangular pulses of a 1-ms width per phase) at paresthesia levels or higher depending on each participant's comfort level during assisted stepping with the Lokomat 6 Pro, a robotic device that helps the legs step and provides as needed body weight support. A total of 20 sessions (weekdays excluding weekends and holidays), each for 1 hour, will be administered.

Device: Multisite transspinal stimulation during robotic gait training

Interventions

Multisite transspinal stimulation at rest DEVICE

The intervention, combined cervical and lumbar transspinal stimulation, will be used for the first time to reconnect the spared neuronal pathways of the injured human spinal cord. The intervention will be administered while at rest lying on the back or during robotic gait training. Cervical and lumbar transspinal stimulation will be delivered via surface active electrodes placed on the back of the neck and on low back, and four returning electrodes placed on each clavicle and iliac crest.

Also known as: transcutaneous spinal cord stimulation, transspinal stimulation, robotic gait training, locomotor training, non-invasive spinal cord stimulation

Multisite transspinal stimulation at rest

Multisite transspinal stimulation during robotic gait training DEVICE

The intervention, combined cervical and lumbar transspinal stimulation, will be administered during robotic gait training. Cervical and lumbar transspinal stimulation will be delivered via surface active electrodes placed on the back of the neck and on low back, and four returning electrodes placed on each clavicle and iliac crest while participants step with the help of the Lokomat 6 Pro, a robotic device that helps the legs step. Locomotor training will depend on the ability of each participant to step without foot dragging. Over the training course, we will adjust the body weight support, ankle straps position, and leg guidance force. The tension of the ankle straps will be adjusted based on the right and left tibialis anterior muscle strength evaluated every 2 weeks. Body weight support and leg guidance force will be adjusted based on presence or absence of knee buckling during standing.

Also known as: locomotor training, body weight supported assisted step training

Multisite transspinal stimulation during robotic gait training

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• In good general health as evidenced by medical history.
• Diagnosed with incomplete SCI (AIS B, C, D).
• Bone mineral density of the hip (proximal femur) T-score \<3.5 SD from age- and gender-matched normative data.
• Lesion above thoracic (T) 10 to ensure absent lower motoneuron lesion.
• The presence of soleus and FCR H-reflexes.
• Absent permanent ankle joint contractures prevent passive or active ankle movement because corticospinal and spinal excitability is based on the ankle angle. The ankle straps of the Lokomat also require 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.

You may not qualify if:

• Supraspinal lesions.
• Neuropathies of the peripheral nervous system.
• Significant degenerative neurological disorders of the spine or spinal cord.
• Diagnosed with AIS A.
• Presence of pressure sores.
• Advanced urinary tract infection.
• 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, pacemakers, implanted infusion device, and/or implanted stimulators of any type and purpose will be excluded to avoid their malfunction due to stimulation.

Sponsors & Collaborators

• Maria Knikou, PT, MBA, PhD: lead

Study Sites (1)

College of Staten Island (Building 5N-218)

Staten Island, New York, 10314, United States

RECRUITING

Related Publications (9)

• Knikou M, Mummidisetty CK. Locomotor training improves premotoneuronal control after chronic spinal cord injury. J Neurophysiol. 2014 Jun 1;111(11):2264-75. doi: 10.1152/jn.00871.2013. Epub 2014 Mar 5.

  PMID: 24598526 BACKGROUND

• Smith 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.

  PMID: 25205562 BACKGROUND

• Knikou M, Smith AC, Mummidisetty CK. Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury. J Neurophysiol. 2015 Apr 1;113(7):2447-60. doi: 10.1152/jn.00872.2014. Epub 2015 Jan 21.

  PMID: 25609110 BACKGROUND

• Murray LM, Knikou M. Remodeling Brain Activity by Repetitive Cervicothoracic Transspinal Stimulation after Human Spinal Cord Injury. Front Neurol. 2017 Feb 20;8:50. doi: 10.3389/fneur.2017.00050. eCollection 2017.

  PMID: 28265259 BACKGROUND

• Islam MA, Pulverenti TS, Knikou M. Neuronal Actions of Transspinal Stimulation on Locomotor Networks and Reflex Excitability During Walking in Humans With and Without Spinal Cord Injury. Front Hum Neurosci. 2021 Feb 18;15:620414. doi: 10.3389/fnhum.2021.620414. eCollection 2021.

  PMID: 33679347 BACKGROUND

• Zaaya M, Pulverenti TS, Knikou M. Transspinal stimulation and step training alter function of spinal networks in complete spinal cord injury. Spinal Cord Ser Cases. 2021 Jul 3;7(1):55. doi: 10.1038/s41394-021-00421-6.

  PMID: 34218255 BACKGROUND

• Sayed Ahmad AM, Zaaya M, Harel NY, Knikou M. Transspinal stimulation preceding assisted step training reorganizes neuronal excitability and function of inhibitory networks in spinal cord injury: A randomized controlled trial. medRxiv [Preprint]. 2025 Jun 12:2025.06.11.25329338. doi: 10.1101/2025.06.11.25329338.

  PMID: 40585100 BACKGROUND

• Knikou M, Murray LM. Repeated transspinal stimulation decreases soleus H-reflex excitability and restores spinal inhibition in human spinal cord injury. PLoS One. 2019 Sep 26;14(9):e0223135. doi: 10.1371/journal.pone.0223135. eCollection 2019.

  PMID: 31557238 BACKGROUND

• Sayed Ahmad AM, Skiadopoulos A, Knikou M. Interactions between arm and leg neuronal circuits following paired cervical and lumbosacral transspinal stimulation in healthy humans. Exp Brain Res. 2024 Sep;242(9):2229-2239. doi: 10.1007/s00221-024-06891-y. Epub 2024 Jul 22.

  PMID: 39034329 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• MARIA KNIKOU, PT, MBA, PhD

  City University of New York, College of Staten Island

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MARIA KNIKOU, PT, MBA, PhD

CONTACT

+1-718-982-3316; maria.knikou@csi.cuny.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Researchers who will perform data reduction, data analysis and statistical analysis of the data.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Senior Research Scientist

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: October 2, 2025
• Study Start: February 19, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Study Protocol and Statistical Analysis Plan (SAP) will be shared at the completion of the clinical trial.
• Access Criteria: IBD and supporting information will be available to the investigators of the clinical trial, institutional review board (IRB) committees, and the funder. IBD and supporting information will be available to other researchers upon completion and publication of the results of the clinical trial upon written request to the Principal Investigator. The investigators of the clinical trial, institutional review board (IRB) committees, and the funder will have access to coded muscle activity and compound muscle action potentials stored as Spike 2 or LabView data files in a password-protected computer, as well as information entered in handwriting in experimental forms. Clinical research evaluation tests are logged in a printed document and saved in a locked file cabinet separate from medical records and signed consent forms. All data, digital or written in forms, are saved with the code given to each participant

Locations

US (1)