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

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ClinicalTrials.gov Identifier: NCT04077346
Recruitment Status : Enrolling by invitation
First Posted : September 4, 2019
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Andrea L. Behrman, PhD, PT, University of Louisville

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.


Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Device: Biostim-5 transcutaneous spinal stimulator Other: Transcutaneous Spinal Stimulator + Activity Based Locomotor Training Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neuromodulation of Spinal Locomotor Circuitry to Elicit Stepping After Pediatric Spinal Cord Injury
Actual Study Start Date : April 12, 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Device: 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


Other: 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.




Primary Outcome Measures :
  1. Movement observation (live observation) with video review of the ability to initiate and take an independent, voluntary step from a position of standing. [ Time Frame: Change in ability to voluntarily step comparing pre-stimulation to during and post stimulation during session 1, session 2, session 3, and session 4 within 1 month of initiation and at session 1, 20, 40, and 60, within a 4 month period ]
    Ability to take step independently with minimal or no external support. Participant can use a walker or other assistive device for balance and support. The participant will stand independently and lift a limb/foot off the ground and step forward making the same foot contact the ground in front as when taking a first step. This will be measured via movement observation by a licensed physical therapist and videotaped. A single step is all that is required. If more than one step is observed, this information will be documented and also videotaped. No manual assistance will be provided during the assessment for a voluntary step. The achievement of an independent step, foot leaves the ground and is placed forward, is the only criteria for the 'step'.

  2. Electromyography (EMG) recording of lower extremity and trunk muscles [ Time Frame: Change in EMG: pre-stimulation compared to during stimulation during session 1, session 2, session 3, and session 4 within 1 month of initiation and at session 1, 20, 40, and 60 within a 4 month period ]
    Measurement of muscle and nerve functions. The muscle activities are reported in microvolts.

  3. Angular excursions of lower extremity [ Time Frame: Change in limb angle excursions: Pre-stimulation compared to during-stimulation during session 1, session 2, session 3, and session 4 within 1 month of initiation and at session 1, 20, 40, and 60 within a 4 month period ]
    Degrees of flexion/extension, adduction/abduction, and rotation, using wireless motion sensors.



Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04077346


Locations
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United States, Kentucky
Department of Neurosurgery, University of Louisville
Louisville, Kentucky, United States, 40202
Sponsors and Collaborators
University of Louisville
Investigators
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Principal Investigator: Andrea L Behrman, PT, PhD University of Louisville
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Responsible Party: Andrea L. Behrman, PhD, PT, Professor, University of Louisville
ClinicalTrials.gov Identifier: NCT04077346    
Other Study ID Numbers: 19.0844
First Posted: September 4, 2019    Key Record Dates
Last Update Posted: May 4, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Andrea L. Behrman, PhD, PT, University of Louisville:
Pediatric-onset
Transcutaneous spinal stimulation
Stepping
Additional relevant MeSH terms:
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Spinal Cord Injuries
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Glycoprotein, Klebsiella pneumoniae
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs