Multisite Transspinal Stimulation for Augmenting Recovery in Spinal Cord Injury

Maria Knikou, PT, MBA, PhD

Status: Enrolling

Conditions: Spinal Cord Injuries (Complete and Incomplete)

Treatments: Device: Multisite transspinal stimulation during robotic gait training; Device: Multisite transspinal stimulation at rest

Study type: Interventional

Funder types: Other

Identifiers

NCT07204184

C41217GM (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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36 participants in 2 patient groups

Multisite transspinal stimulation at rest

Active Comparator group

Description:

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.

Treatment:

Device: Multisite transspinal stimulation at rest

Multisite transspinal stimulation during robotic gait training

Active Comparator group

Description:

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.

Treatment:

Device: Multisite transspinal stimulation during robotic gait training