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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
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.
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.
College of Staten Island (Building 5N-218)
Staten Island, New York, United States
RECRUITINGSoleus 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Before and 2 days after all intervention sessions are completed.
2-Minute Walk Test
The 2-Minute Walk Test is a physical assessment measuring aerobic capacity and endurance. Participants will walk with or without assistive devices as far as possible for two minutes in a hallway. The total distance walked is recorded, and will be compared to normative values for the participant's age and gender to identify potential limitations or track progress over time. There is currently no single established Minimal Clinically Important Difference for the 2-minute walk test in people with spinal cord injury. However, a recent study showed that in the subacute phase of rehabilitation a 2-Minute Walk Test Minimal Clinically Important Difference is considered when the increase is 31 meters. However, other research studies indicate that the Minimal Clinically Important Difference can vary significantly depending on the specific patient population, rehabilitation stage, disability level, and age.
Time frame: Before and 1-day after all intervention sessions are completed.
10-Meter Walk Test
The 10-Meter Walk Test is a performance measure and assesses the walking speed in meters per second over a short duration. Participants will walk 10 meters and the time needed to cover the 10 meters will be recorded. The minimal clinically important difference for the 10-meter walk test in spinal cord injury is approximately 0.13 m/s, a value established for individuals with incomplete SCI within one year of injury. This means that recovery of walking ability will be based on when the speed is improved by 0.13 m/s.
Time frame: Before and 1-day after all intervention sessions are completed.
Sexual function
Participants will complete a brief questionnaire on sexual function before and after intervention. The questionnaire is the International Spinal Cord Injury sexual function for male and female. The answers to the questions include: normal, reduced/altered, absent, and unknown/not applicable. Improvement from the intervention will be considered when more "normal" answers replace the "reduced-absent or absent" answers.
Time frame: Before and 1-day after completion of all intervention sessions.
Bladder function
The Overactive Bladder Symptom Score (OABSS) questionnaire will be answered by the participants before and after intervention to establish recovery or changes of the bladder function. The maximum score is 15 and the minimum score is 0. The smaller the score the better the outcome.
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Time frame: Before and 1-day after completion of all intervention sessions.
Bowel function
The University of Michigan Spinal Cord Injury Model Systems for Bowel function questionnaire will be used to establish recovery or changes. The answers are descriptive including yes or no or at least daily or never. A number 1 will be given to the answer that represents the least impact of bowel function on the quality of life and satisfaction. When the sum of scores is lower by at least 20% after the intervention, it will be regarded as improvements in bowel function.
Time frame: Before and 1-day after all intervention sessions are completed.
Modified Ashworth Scale
The Modified Ashworth Scale assesses spasticity in the lower extremity. The investigators will apply a quick manual stretch to the ankle. A score from 0 to 4 will be given, where 0 indicates no increase in tone and 4 signifies complete rigidity. A score of 1 or 1+ indicates a slight increase in tone with a catch, while 2 means a marked increase, and 3 signifies a considerable increase that makes passive movement difficult. The maximum score is 4 and the minimum score is 0. The lower the score the better the outcome or recovery. A minimal clinically important difference for the Modified Ashworth Scale is 0.45 for the lower extremity.
Time frame: Before and 1-day after all interventions are completed.