Multisite Transspinal Stimulation for Augmenting Recovery in Spinal Cord Injury

NCT ID: NCT07204184

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2028-06-30

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.

Detailed Description

The main objective of this hypothesis-based and need-driven clinical research trial is to develop novel rehabilitation strategies and impact clinical practice and care for people with spinal cord injury (SCI). The investigators will use non-invasive transspinal stimulation over the cervical and lumbosacral enlargements, the spinal location of arm and leg motor circuits, to augment the benefits of locomotor training and improve recovery of standing and walking ability in individuals with SCI. This trial is a pilot (or small-scale) clinical trial on cervical and lumbosacral transspinal stimulation administered alone at rest or during assisted step training in people with SCI to establish safety and efficacy.

The investigators' specific aims are as follows:

1. Determine the underlying physiological actions of paired cervical and lumbosacral transspinal stimulation in people with and without SCI. To address Specific Aim 1, in 12 people with incomplete SCI (AIS B, C, D) and 12 healthy control subjects (age and gender match) we will establish the effects of a) cervical transspinal stimulation on soleus H-reflexes and leg transspinal evoked potentials (TEPs), and the effects of lumbosacral transspinal stimulation on flexor carpi radialis (FCR) H-reflexes, and arm TEPs at rest; and b) the effects of cervical and lumbosacral paired transspinal stimulation on joint coordination and muscle synergies during walking on a motorized treadmill (healthy controls) or with a robotic gait system training (Lokomat) in participants with SCI.

2. Determine if cervical and lumbosacral transspinal stimulation reconnects the injured human spinal cord, strengthens the weak remnant neuronal pathways, and augments the benefits of locomotor training. To address Specific Aim 2, a total of 24 people with incomplete SCI (AIS B, C, D) will be enrolled. Half will receive cervical and lumbosacral transspinal stimulation at rest. The other half of participants will receive cervical and lumbosacral transspinal stimulation during assisted stepping with a robotic gait system (Lokomat 6 Pro®).

Both groups will receive 20 sessions (5 sessions/week) of 1-hr duration each. Cervical and lumbosacral transspinal stimulation will be delivered at 30 Hz at or above paresthesia intensities based on each participant's comfort levels. For both groups, the investigators will establish safety based on adverse events, and efficacy based on clinical assessments and neurophysiological biomarkers. Before and after the intervention the investigators will 1) establish changes in non-somatic vital bladder, bowel, and sexual body functions, 2) perform clinical assessments of spasticity, standing and walking ability, and 3) perform state-of-the-art experiments to establish changes in neurophysiological biomarkers.

The investigators will use neurophysiological biomarkers to probe actions of the proposed intervention (cervical and lumbosacral transspinal stimulation), use combination of interventions, and address safety and efficacy of intervention via adverse events and neurophysiological biomarkers. Furthermore, the investigators will 1) identify and validate biomarkers for diagnosis, prognosis, and evaluation of treatment efficacies, and 2) maximize the function of the residual neural circuitry, including harnessing neuroplasticity and recovery to improve function after SCI.

Conditions

Spinal Cord Injuries (Complete and Incomplete)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Multisite transspinal stimulation at rest

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.

Group Type: ACTIVE_COMPARATOR

Multisite transspinal stimulation at rest

Intervention Type: 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.

Multisite transspinal stimulation during robotic gait training

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.

Group Type: ACTIVE_COMPARATOR

Multisite transspinal stimulation during robotic gait training

Intervention Type: 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.

Interventions

Multisite transspinal stimulation at rest

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.

Intervention Type: DEVICE

Multisite transspinal stimulation during robotic gait training

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.

Intervention Type: DEVICE

Other Intervention Names

transcutaneous spinal cord stimulation; transspinal stimulation; robotic gait training; locomotor training; non-invasive spinal cord stimulation; locomotor training; body weight supported assisted step training

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Maria Knikou, PT, MBA, PhD

OTHER

Sponsor Role: lead

Responsible Party

Maria Knikou, PT, MBA, PhD

Professor, Senior Research Scientist

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

MARIA KNIKOU, PT, MBA, PhD

Role: PRINCIPAL_INVESTIGATOR

City University of New York, College of Staten Island

Locations

College of Staten Island (Building 5N-218)

Staten Island, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

MARIA KNIKOU, PT, MBA, PhD

Role: CONTACT

maria.knikou@csi.cuny.edu

+1-718-982-3316

Facility Contacts

MARIA KNIKOU, PT, MBA, PhD

Role: primary

maria.knikou@csi.cuny.edu

718-982-3316

References

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.

Reference Type: BACKGROUND

PMID: 24598526 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25205562 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25609110 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28265259 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33679347 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34218255 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 40585100 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31557238 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 39034329 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

C41217GM

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

C41217GM

Identifier Type: -

Identifier Source: org_study_id