Neuromodulation of Spinal Locomotor Circuitry to Elicit Stepping After Pediatric Spinal Cord Injury

NCT ID: NCT04077346

Last Updated: 2025-02-26

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-12
• Study Completion Date: 2026-01-31

Brief Summary

Spinal cord injury (SCI) results in damage to the descending neural pathways and leads to the immediate dysfunction of multiple physiological systems below the level of injury. Like adults, children with SCI suffer from neuromuscular paralysis which results in the inability to sit, stand, and walk. Current therapeutic interventions largely aim to compensate for paralysis to achieve mobility based on the assumption that damage to the central nervous system is permanent and irreversible, e.g. use of braces, standers, and wheelchairs. The objective of this proposal is to investigate the use of transcutaneous spinal stimulation (TcStim) to enable stepping in children with chronic SCI.

The investigators will recruit 8 participants, ages 4-12 years with chronic, acquired SCI, T10 and above and non-ambulatory. The aims of this proposal are to 1) investigate the mechanisms of locomotor-specific regulation in the spinal neural circuitry of children with acquired SCI using single vs. multi-site TcStim, 2) investigate the capacity of the lumbosacral spinal cord for integration of task-specific input (e.g. load, speed) during facilitated stepping with and without TcStim, and 3) investigate the training effects of TcStim on the ability to step. Outcomes will provide a necessary initial step in the translation of scientific findings for neuromodulation from adults with SCI to children.

Detailed Description

Like in adults, children with spinal cord injury (SCI) in children suffer from neuromuscular paralysis which results in the inability to sit, stand, and walk. Current therapeutic interventions, e.g. leg braces, wheelchairs, largely aim to compensate for paralysis based on the assumption that damage to the central nervous system is permanent and irreversible.The discovery of the "intelligent" spinal cord, known as the central pattern generator (CPG), has demonstrated that complex neuronal networks are capable of generating rhythmic and coordinated motor patterns and has set forth a major paradigm shift in the investigators expectation of the possibility for recovery even with severe SCI. Studies have demonstrated, first, that after SCI, the CPG can be "accessed", reactivated, and retrained via sensory feedback arising from the muscles and joints during activity-based locomotor training (AB-LT). Second, application of epidural and transcutaneous stimulation (TcStim) to the spinal cord below the level of lesion can augment the neuromuscular capacity for voluntary movement, standing and stepping in adults with chronic motor complete SCI. While neural mechanisms for stepping regulation have been demonstrated in adults testing single vs. multi-site stimulation, this inherent capacity must be examined in children with SCI. Similarly, the addition of stimulation during AB-LT in adults with motor complete SCI has resulted in remarkable recovery of over ground walking. The immediate and long-term response of such combined therapeutic exposure and subsequent training has yet to be examined in children. Children with SCI may not only benefit from these novel therapeutic approaches but also demonstrate greater improvements in neuromuscular recovery due to inherent plasticity. The investigators' preliminary work has demonstrated the safety and feasibility of TcStim in children with SCI. Therefore, the specific aims of this proposal are to 1) investigate the spinal mechanisms for regulation of locomotor circuitry in children with SCI using TcStim, 2) assess whether the combination of task-specific AB-LT and TcStim can acutely potentiate lower limb muscle activity during facilitated stepping, and 3) assess training effects of TcStim combined with AB-LT to promote stepping capacity in non-ambulatory children with SCI.

For this pilot study 8 participants, ages 4-12 years with chronic, acquired SCI, T10 and above and non-ambulatory will be recruited.

For Aim 1, n=8, TcStim will be used to stimulate a single or multi site spinal levels to produce stepping/locomotor activity in lower limbs. Knee, hip, ankle kinematics and electromyography (EMG) of the lower limb muscles in response to stimulation will be recorded during the experiments. The investigators will determine the stimulation parameters that produce rhythmic movements with the greatest increase in lower limb joint excursions as well as EMG amplitude.

For Aim 2, n=8, TcStim will be delivered while participants attempt to take a step overground and while stepping on a computerized treadmill with an overhead partial body weight support (BWS) system. The participants will be stepped at age-appropriate speeds and BWS optimizing the stepping kinematics. The speed and the amount of body weight support provided during the assessment as well as full body kinematics and EMG signals from trunk and lower limb muscles will be recorded during facilitated stepping with and without TcStim.

For Aim 3, n=6, participants will receive 60 sessions of AB-LT+Tcstim. Ability to initiate and complete a step overground with and without stimulation along with full body kinematics and electromyographic (EMG) signals from trunk and lower limb muscles will be recorded at baseline, 20, 40, and 60 sessions of the combined therapy of AB-LT plus TcStim.

Conditions

Spinal Cord Injuries

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transcutaneous Spinal Stimulation- Acute and with Training.

For Aim 1: Participants will receive transcutaneous stimulation (TcStim) in supine or side lying position at a single or multi site spinal levels to produce stepping/locomotor activity in lower limbs.

For Aim 2: TcStim will be delivered while participants are stepping on a computerized treadmill with an overhead partial body weight support (BWS) system and while stepping overground.

For Aim 3: Participants will first receive a combination of Activity-based locomotor training (AB-LT)+TcStim for 60 sessions.

Group Type: EXPERIMENTAL

Biostim-5 transcutaneous spinal stimulator

Intervention Type: DEVICE

Transcutaneous spinal stimulation (TcStim): The 5-channel stimulator capable of generating (41) pain-free biphasic rectangular waveform of 0.3- to 1.0-ms pulses with a frequency of 5-10 kHz will be used to stimulate at single or multi-site spinal levels.

TcStim will be delivered in combination with activity based locomotor training in 5 - 10 minute of stimulation at sub-motor threshold daily (5x/week) for 60 sessions

Transcutaneous Spinal Stimulator + Activity Based Locomotor Training

Intervention Type: OTHER

Participants will receive a combination of Activity-based locomotor training (AB-LT)+TcStim daily (5x/week) for 60 sessions and will consist of a minimum of 55-60 min on the TM for facilitated standing/stepping followed by 30 min of activities off TM in sitting, standing, or stepping.

Interventions

Biostim-5 transcutaneous spinal stimulator

Transcutaneous spinal stimulation (TcStim): The 5-channel stimulator capable of generating (41) pain-free biphasic rectangular waveform of 0.3- to 1.0-ms pulses with a frequency of 5-10 kHz will be used to stimulate at single or multi-site spinal levels.

TcStim will be delivered in combination with activity based locomotor training in 5 - 10 minute of stimulation at sub-motor threshold daily (5x/week) for 60 sessions

Intervention Type: DEVICE

Transcutaneous Spinal Stimulator + Activity Based Locomotor Training

Participants will receive a combination of Activity-based locomotor training (AB-LT)+TcStim daily (5x/week) for 60 sessions and will consist of a minimum of 55-60 min on the TM for facilitated standing/stepping followed by 30 min of activities off TM in sitting, standing, or stepping.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Children with acquired, upper motor neuron (T10 and above) SCI, traumatic and non-traumatic,
• Chronic injury, defined as greater than one year post injury
• Age 4-12 years,
• Discharged from inpatient rehabilitation,
• Unable to stand, walk, or initiate steps.

Exclusion Criteria

• Botox use within past 3 months
• Current oral baclofen use,
• Baclofen pump in use,
• Musculoskeletal impairment limiting range of motion, unhealed fracture or other medical complication limiting participation,
• Prior surgery for scoliosis, post SCI
• Congenital SCI,
• Total ventilator dependence.

For Aim 3, additional exclusionary criteria are:

• Unwilling or unable to wean from baclofen during training,
• Use of braces (trunk or lower limb brace).

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kentucky Spinal Cord and Head Injury Research Trust and Board

UNKNOWN

Sponsor Role: collaborator

Kosair Charities, Inc.

OTHER

Sponsor Role: collaborator

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Andrea L. Behrman, PhD, PT

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea L Behrman, PT, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville

Locations

Department of Neurosurgery, University of Louisville

Louisville, Kentucky, United States

Countries

United States

Other Identifiers

19.0844

Identifier Type: -

Identifier Source: org_study_id