Louisville, Kentucky 40202


Purpose:

The overall aim is to assess whether task specific locomotor training and spinal cord electrical stimulation (SCES) can induce neural reorganization of the functionally isolated human spinal cord to improve standing and stepping in individuals with functionally complete SCI. The investigators propose that locomotor training will result in generation of more effective standing and stepping efferent patterns by restoring phase dependent modulation of reflexes and reciprocal inhibition, reducing clonus and mediating interlimb coordination. The investigators propose that the SCES will optimize the physiological state of the spinal cord interneuronal circuitry compromised by compensating for loss of supraspinal input for the retraining of these tasks. The proposed studies will allow us to gather critical information using commercially available electrodes to design the more advanced multi-electrode array technique that will be adaptive and conceivably be effective in a wider range of patient populations. The current electrodes used in this study will serve two objectives: 1) to improve standing and stepping with the combination of epidural stimulation and locomotor training in individuals with functionally complete SCI; and 2) to provide critical information for the development of more advanced electrodes.


Study summary:

SCREENING: Evaluation Tests and Pre-Training (1st consent) Dr. Harkema will determine study eligibility based on the inclusion and exclusion criteria and in accordance with the medical recommendation of Dr. Boakye & Dr. Williams. Participating in the initial portion of the study does not guarantee their eligibility for surgical implantation and epidural stimulation. These individuals will not be enrolled in any other experimental studies unless approved by the principal investigator. The investigators will evaluate the research participants for: 1) functional neurophysiological assessment (FNPA); 2) nerve conduction study (NCS); 3) somatosensory evoked potentials (SEP); 4) sympathetic skin responses (SSR); 5) efferent motor activity during standing; 6) efferent motor activity during stepping and 7) reflexes during supine, prone, sitting and standing; 9) bladder function; 10) CV function. The FNPA, NCS, SEP and SSR will be performed while the research participant is lying supine on a mat. The efferent motor assessments will be performed in the body weight support treadmill with the assistance of trainers at the hip and at each leg. After completion of these evaluations, participants will undergo 80 sessions of step/stand training. The investigators will repeat the FNPA, NCS, SEP, SSR, reflexes, bladder function, CV function and assessment of the efferent motor activity during standing and stepping after the completion of the 80 training sessions to quantify that no motor pattern changes are achievable with LT alone. Drs. Harkema, Williams, Park and Boakye will meet to discuss the results of the preliminary testing and evaluate if the participant is eligible for surgical implantation for SCES. FULL ENROLLMENT: Surgery + Epidural Stimulation + Training (2nd consent) If after evaluating the results, the study investigators determine that the participant is an appropriate candidate for surgery and epidural stimulation, the participants will be asked to sign an additional consent form. The surgery will be performed at University Hospital to insert the epidural stimulating electrodes. The lead wires will be tunneled subcutaneously to exit 5 centimeters from the incision site. The implantable neurostimulator will be internalized and the connecting wires for the implanted electrodes will be tunneled under the skin and connected with the battery generator that will be placed in the abdominal area. We will repeat the experiments beginning 2-14 days after the surgery both with and without stimulation for 10 - 14 days. During the first two weeks after the surgery, the research participants may be hospitalized at Frazier Rehab Institute to monitor the incision site. We will also identify appropriate stimulation parameters for inducing stepping and standing in combination with manual assistance using body weight support on a treadmill (BWST). Following discharge from inpatient or recovering at home the individuals will be seen at Frazier Rehab Institute on a daily basis for testing and LT. We will evaluate the combination of epidural stimulation with manual step/stand training. This stage will be conducted over six-eight months. During training, the patients will be provided with epidural stimulation using the parameters defined in Stage 1. Testing (FNPA, MEP, SSR and efferent motor activity) may be performed weekly. Locomotor Training: Every research participant will be slowly acclimated to the body weight support system to make him/her feel comfortable in an upright position. This may help the research participant avoid experiencing a lowered blood pressure or dizziness. However, if these conditions should occur, the research participant would immediately be unhooked from the system, removed from an upright position, the legs elevated, and the blood pressure monitored. Stepping bouts are relatively short in duration, thus an increase in respiration as well as an increase in heart rate or blood pressure will generally last for only a couple of minutes. Each research participant will be closely monitored through each experiment and training session. Standing or stepping will immediately halt once the research participant feels tired or winded. Blood pressures & heart rates will be monitored by the PT or trained staff regularly during each training session. Continuous blood pressure, breathing rate, and temperature may be monitor with sensors throughout the training sessions and experiments. Participants may train 2x a day, they will train both to stand and step on the same day. The sessions will only be counted if the progression criteria are met, for example independence minutes or weight-bearing minutes. Before and after every experiment and training session, a physical therapist (PT) or research staff member will examine the research participant's skin for irritations and abrasions. If skin irritations or abrasions are caused by the electrodes, harness position or hand placements of trainers, electrode, the harness and hand placement will be modified appropriately. Further, the PT will constantly monitor the research participant's skin and muscle for signs of muscle strain, joint sprain and skin irritation (e.g. temperature and redness). Dr. Harkema & the PT will continually assess the appropriate BWS & continuously monitor manual assistance by trainers to avoid joint sprain and fracture. Further, continuous monitoring of the research participant will be conducted by the staff for potential injuries. For example, signs of skin redness, swelling of joints, or spasticity can be indicators of injury when research participants have impaired sensation. Research participants will also be stretched by the PT or trained staff member before and after each training session to prevent injury. If any signs of risks or discomfort are noted, the experiment or training session will be immediately discontinued. If any complications arise, the stand or step training will immediately stop and Dr. Williams will immediately be informed. In addition, the research participant's primary care provider will be notified as necessary. Dr. Williams will be the medical advisor for the research participants throughout the LT segment of this study. Dr. Boakye will oversee all surgical related issues for the research participants. After the training period has ended, patients will be followed by Drs Boakye/Williams and Harkema every 3-6 months for a total of 3 years following surgery. After 3 years the patients will be followed up by Drs Boakye/Williams and Harkema every six months for continued long-term care until the device is explanted or the device is approved for stepping and standing in spinal cord injury. Follow-up neurological examination for the purpose of this study will be incorporated into each clinic visit. The decision to continue to maintain the stimulators or remove them will be made during these follow-up visits. Dr. Harkema and the research team might ask the participant to return for training in the laboratory for an extended time (80-100 sessions) during the follow up period. Training (stand or step) will be designed to optimize parameters and built to improve on previous training. During this time participants might be asked to functional train with the combination of our adaptive epidural stimulation strategy with manual LT. During training, the participants will be provided with ES using the parameters determined using the computation learning method which is developed during phase 2 described below. Design including all survey instruments, questionnaires, etc. SCREENING CONSENT: Stage 1A: Standing and stepping interventions FULL ENROLLMENT CONSENT: Stage 1B: Surgical Procedure Stage 1C: Stimulation with standing and stepping interventions Stage 2A: Stimulation with standing and stepping assessments Stage 2B: Adaptive Multielectrode Epidural Stimulation and LT Stage 1A: Standing and stepping interventions Prior to the initial surgery the participant will undergo 80 sessions of step/stand training (screening). We will evaluate the research participants for 1) functional neurophysiological assessment (FNPA), 2) nerve conduction study (NCS); 3) somatosensory evoked potentials (SEP); 4) sympathetic skin responses (SSR), 5) efferent motor activity during standing, 6) efferent motor activity during stepping and 7) reflexes during supine, prone, sitting & standing before the initiation of training, 9) bladder function, 10) CV function, 11) MRI of the spinal cord. Each of these measurements will take between 1 and 4 hours. We will repeat these measurements at the end of the initial 80 training sessions. Body Weight Support on a Treadmill (BWST). The BWST system's primary purpose is to provide body weight support and control the vertical force exerted on the legs. This also provides trunk stability and prevents the research participant from falling during standing or stepping. The BWST is a device used to assist research participants with neurologic injuries during standing and stepping. Research participants wear a modified parachute harness connected to a cable, which links to the overhead pneumatic support system. We can input the desired amount or percentage of support, and the cable will lift the specified weight from the research participant, leaving less weight to be supported by the research participant. Our laboratory uses a pneumatic, closed loop force controlled system hoist that provides weight support and controls ground contact force patterns. If the actual support varies from the desired support, the system is designed to adjust the pressure in the pneumatic cylinder to equalize the set and actual support force. Due to the constant feedback, this system provides safety and allows for the center of mass movement during stepping. Functional Neurophysiological Assessment (FNPA). Research participants will lie supine on a mat with legs in an extended position. They will be asked to perform a series of eight exercises. 1) Relaxation for 5 minutes. 2) Reinforcement maneuvers. 3) Voluntary motor tasks. 4) Passive movements. 5) Tendon taps.. 6) Manual clonus elicitation. 7) Tonic vibratory response. 8) Withdrawal suppression. The plantar surface of the foot will be stimulated as is done to elicit the Babinski sign. The stimulus will be delivered with a rod. For the initial three trials subjects will be instructed to relax and allow the leg to jump should it do so. For the subsequent three trials subjects will be instructed to relax and prevent the leg from jumping. Nerve Conduction Study (NCS) - Nerve conduction is recorded through surface electrodes to measure conduction in the peripheral nervesSurface EMG electrodes are placed at a known distance away from the stimulating electrode over the muscle(s) innervated by the studied nerve (soleus, tibialis anterior, extensor digitorum longus). Ground straps are placed on thighs. Repeated single-pulse electrical stimulation is delivered at very low intensities for the recorded muscles for each of the three nerves evaluated. Stimulation delivery rates will not exceed 2 per second. Somatosensory evoked potentials (SEPs) - SEP are recorded through surface electrodes to measure conduction in the peripheral nerves, cervical and lumbosacral spinal cord, deep brain structures, and sensory cortex. Surface EMG electrodes are placed over the adductor pollicis brevis and soleus muscles. Stimulation electrodes are placed over the median nerve at the wrist and tibial nerve in the popliteal fossa of the right and left upper and lower limbs. Ground straps are placed on the forearms and thighs. Repeated single-pulse electrical stimulation is delivered at intensities of 1 and 1.5 times motor threshold for the recorded muscles for each of the four nerves evaluated. Averaged responses for up to 256 stimuli will be recorded for each of these two intensities for the right and left median and tibial nerves. Simultaneous bilateral stimulation will be applied if no recognizable responses are recorded from the scalp leads. Stimulation delivery rates will not exceed 2 per second. Sympathetic Skin Response (SSR). The disruption to the spinal autonomic pathways will be measured by electrophysiological recordings in the supine position, with the room temperature (21-25 deg C). Subjects will rest supine for at least 10 min before the beginning of the examination. Self-adhesive electrodes will be applied to the palmar and dorsal surfaces of the hands and plantar and dorsal surfaces of the feet. The median nerve will be stimulated (0.2 ms duration, 10-20mA intensity) and 10 SSR samples will be recorded bilaterally from both hands and feet (band pass of 3Hz to 3 kHz). The average latency (ms) and amplitude (mV) of the 10 SSRs will be calculated. Efferent motor activity during standing. During the testing the research participants will be placed on the treadmill (upright) & suspended in a harness by an overhead cable at the maximum load at which knee buckling and trunk collapse can be avoided (i.e. BWST). All participants will stand at their optimized body weight load (BWL) and joint kinematics and limb load will be consistently maintained by manual assistant by trainers. All trainers are careful to provide manual assistance only when needed. A trainer positioned behind the research participant will aid in pelvis and trunk stabilization, by applying anterior forces at the pelvis and/or posterior forces at the shoulders, ensuring that the trunk and pelvis are not flexed or hyper-extended. Research participants will take a break and rest at any time they feel the need to during the session. Efferent motor activity during stepping. During the testing the research participants will be placed on the treadmill in an upright position and suspended in a harness by an overhead cable at the maximum load at which knee buckling and trunk collapse can be avoided (i.e. the BWST). All trainers are careful to provide manual assistance only when needed. A trainer positioned behind the research participant will aid in pelvis and trunk stabilization, as well as appropriate weight shifting and hip rotation during the step cycle. The trainer will ensure that the trunk and pelvis are not flexed or hyper-extended during stepping, and that the weight is shifted from the ipsilateral limb to the contralateral limb simultaneous with ipsilateral swing initiation. Research participants will take a break and rest at any time they feel the need to during the session. Joint kinematics, limb load and treadmill speed will be consistently maintained for each phase of the step cycle during these trials. Reflexes during supine, prone, sitting, and standing. H-reflex elicited at the back or leg muscle. The H-reflex is analogous to the stretch reflex (muscle spindles activate Ia afferents that synapse on alpha-motor neurons), but is elicited by an electrical stimulus to the Ia fibers in the afferent nerve, circumventing the muscle spindle. The H-reflex will be elicited using electrical stimulation to the tibial nerve using an AgCl cathode in the popliteal fossa and a 40-mm-diameter anode placed over the patella. The H-reflex can also be elicited using electrical stimulation from stimulating electrodes placed on the subjects' back. Concurrently we will record EMG from leg muscles using bipolar surface electrodes placed on the muscle bellies. The EMG signals propagate through long shielded wires to custom-built amplifiers (frequency response 20 Hz-10 kHz). The stimulus will be a 1 ms square wave pulse (0.5 Hz - 200 Hz) delivered by a custom-built computer-controlled constant current stimulator. This response will be dependent on the stimulus strength. Eliciting a stimulus with a strength that is just above the threshold for the alpha-motoneurons will also result in direct stimulation of the leg muscle or back, producing the M-wave. The peak to peak amplitude of the H-wave will be plotted versus the peak to peak amplitude of the M-wave. The maximum H-wave amplitude divided by the maximum M-wave amplitude will be calculated. We will use two different reflex protocols to test the long descending propriospinal system. The long propriospinal system will be tested based on H reflex amplitude in the Soleus muscle under conditioning stimulation of ulnaris nerve. The ulnaris nerve will be stimulated via surface electrodes with trains of 3 rectangular pulses (pulse duration: 0.5 ms, pulse interval: 3 ms). In normal subjects the amplitude of H reflex in the Soleus muscle increases when the delay between conditioning and testing stimuli is < 40 ms. A separate protocol will be used to test the reticulospinal connectivity. We will record the audiospinal startle reaction (ASR) (30 msec tone of 90 dB) based on EMG of multiple leg muscles. In addition, we will test the H-reflex facilitation of both the tibialis anterior and Soleus started 50 ms after the sound to peak after 75-125 ms and returned to baseline values after 250 ms. We will also record evoked responses in leg muscles in response to epidural stimulation after conditioning with sound stimulation . The delay between sound stimulation and epidural stimulation will range from 10 - 100 ms. Bladder Function (cystometrogram). Subjects will undergo a cystometrogram to assess bladder capacity and pressure. While the subject is supine a catheter will be inserted in the urethra and advanced into the bladder. The bladder will be filled with saline solution and the pressure will be recorded. Pressure will also be recorded when the bladder is relieved. We may use surface electrodes to measure leg muscle activity during bladder filling and emptying. The test will be performed at an urologist office and does not require sedation or anesthesia. Cardiovascular (CV) Function (Orthostatic Challenge Test). Prior to orthostatic assessments, subjects will lie supine in a temperature controlled room for 20 minutes (rest). Beat-to-beat arterial blood pressure, heart rate, and respiratory rate will be determined in the supine position, and during a 20 minute passive orthostatic challenge (sit up test). Indices of stroke volume, cardiac output and peripheral resistance will be calculated from the blood pressure wave-form. Mean systolic and diastolic arterial blood pressures and heart rate will be calculated at rest and during orthostatic stress. Catecholamine (adrenaline and noradrenaline, nm/l) levels will be measured during rest and orthostatic challenge test. A butterfly catheter (15mm) will be inserted into an antecubital vein before data collection to draw the blood samples, this will allow the collection of blood without additional stress to the participant and activation of catecholamine release by venopuncture. The subject will rest for 20 minutes: a blood sample (10cc) from the antecubital vein will then be taken. A second blood test (10cc) will be obtained following the passive tilt (sit up test). Serum level catecholamine levels will be measured. These data will be correlated with the other indices of CV autonomic function, and severity of injury to spinal autonomic pathways determined by SSR. Lower extremity EMG will be collected simultaneously to make sure that stimulation is not regenerating strong muscle contractions that might result in blood pressure control independent of improvements in CV function. Magnetic Resonance Imaging (MRI). Subjects will undergo a T1- and T2-weighted MRI scan at the T10-S2 levels. Standard sagittal and axial T1-weighted images as well as sagittal T2-weighted turbo inversion recovery spin-echo images will be obtained. The scan will be performed a few days prior to the surgical procedure to determine incision location for appropriate placement in more detail. The decision to implant one or two electrodes will be based on anthropometrical data derived from this scan. If one 16-electrode array does not span across sufficient number or segments a second array will be implanted. Quality of Life, cognitive, autonomic function and sexual function questionnaires. Subjects will be asked to complete a variety of questionnaires focusing on quality of life, disability, cognitive, autonomic and sexual function. Spinal cord injury CDE standard questionnaires will be used in addition to standard quality of life questionnaires. These questionnaires will be administered prior to implantation, at the end of each training paradigm and at each follow up. Stage 1B: Surgical Procedure One or two Medtronic Specify 5-6-5, 16-electrode epidural arrays will be implanted intraoperatively using a single surgery procedure. The surgery will be conducted at University Hospital under a combined regional and general anesthesic. We do not anticipate that the patients will experience any pain during this operation. However, if there is any discomfort, the patients will be administered analgesics by the anesthesiologist and/or the painful area will be infiltrated with local anesthetic. Patients will be placed in the prone position with an incision made in the thoracolumbar area of the spine. We will perform a partial laminectomy at the T11 - T12 interspace providing a site for electrode insertion. The incision will be approximately 2.0 - 2.5 inches. One electrode will be threaded upwards to the T11-L1 segmental levels. If necessary the second electrode will be threaded downward to the S1-S2 segmental levels for placement over the group of spinal cord nuclei where activation of the muscles occurs. Fluoroscopy and neurophysiological parameters will be used to determine the optimal lead placement that will be determined by motor system monitoring. Following the location of optimal lead(s) placement the participant will be rolled to the left lateral decubitus position (right side up) and the surgeon will proceed with the internalization of the implantable neurostimulator into the subcutaneous area of the abdomen. The wires of the implanted epidural electrodes will be tunneled under the skin and connected with the battery generator that will be placed in the abdominal area. If necessary, the same procedure will occur with the participant rolled to the right lateral decubitus position for the internalization of the second neurostimulator. We do not anticipate any increased risks other than the well recognized accepted risks of surgery (infection, bleeding, and anesthesia). Stage 1C: Stimulation procedures and standing and stepping interventions Prior to the surgery we will evaluate the research participants for 1) FNPA, 2) nerve conduction study; 3) SEP; 4) sympathetic skin responses (SSR), 5) efferent motor activity during standing, 6) efferent motor activity during stepping and 7) reflexes during supine, prone, sitting and standing, 9) bladder function, 10) CV function as described above in the screening. We may repeat these measurements beginning 2 weeks after the surgery both +/-stimulation for 10 - 14 days. During the two weeks after the surgery, the research participants may be hospitalized at Frazier Rehab Institute to monitor the incision site. The FNPA, NCS, SEP and SSR will be performed while the research participant is lying supine on a mat. The efferent motor assessments will be performed in the body weight support treadmill with the assistance of trainers at the hip and at each leg. Optimal configurations will also be tested for bladder and CV function. A specific stimulation parameter may be used to assess the influence of epidural stimulation on bladder function and/or CV function. In the case of 9) Bladder function, following its assessment with stimulation the bladder will be filled with saline solution a second time after a 5 minute break. The optimal stimulation configuration for bladder will be used and the pressure will be recorded. The individual will be asked to attempt to empty his/her bladder when the stimulation is ongoing. Pressure will also be recorded when the bladder is relived. This test will take approximately 60 minutes. Similarly the CV function might be assessed without & with stimulation. The orthostatic stress test might be repeated with optimal stimulation for CV control. The butterfly catheter will remain in place from the initial non stimulation test and blood samples will be obtained to same time points to assess if any changes in We will also identify appropriate stimulation parameters for inducing stepping and standing in combination with manual assistance using body weight support on a treadmill (BWST) or overground in the case of standing. Each of the sixteen electrodes will be independently stimulated using subthreshold, tonic, non-patterned epidural stimulation applied at frequencies of 5-50 Hz, and amplitudes of 1-10 V. The specific stimulation parameters will be optimized for each individual to achieve the best motor performance for each task. We may monitor continuous blood pressure, breathing rate and temperature using external sensors pasted over the skins during training sessions or experiments. Stage 2A: Stimulation procedures and standing and stepping assessments Following discharge or following closure of the incision testing and/or training will be conducted 5 times per week for 160 sessions on an outpatient basis. In Stage 2 the individuals will be seen at Frazier Rehab Institute on a daily basis for testing and training. They might be asked to train twice a day (stand and step on the same day) with a 2-4 hour resting period in between. We will evaluate the combination of epidural stimulation with manual step (locomotor) training. This stage will be conducted over four months. During training, the patients will be provided with epidural stimulation using the parameters defined in Stage 1. The participants may be evaluated weekly for 1) FNPA; 2) NCS; 3) SEP; 4) SSR, 5) efferent motor activity during standing, 6) efferent motor activity during stepping and 7) reflexes during supine, prone, sitting and standing, as described above. Following the determination of optimal parameters for standing or voluntary activity, the participant might be given a Patient Programmer to translate weight bearing and stand training and/or voluntary movement with stimulation to the home environment and perform additional training. The programmer will be optimally programmed by the research team in such a way to restrict configuration changes by research participant. A very specific protocol for stimulation and training will be given by the research team and the participant will be required to complete a training log. The research team will collect the home training log from the participant once a week and evaluate the need for changes to the home-based training protocol. Stage 2B: Adaptive Multielectrode Epidural Stimulation and Locomotor Training (LT) Stage 2 will evaluate the combination of our adaptive epidural stimulation strategy with manual step (locomotor) training. During training, the participants will be provided with ES using the parameters determined using the computation learning method in Phase 1. Experimental materials. We will acquire lower extremity & trunk muscles surface EMG activity & kinematics bilaterally during all experimental conditions. We will also use fine-wire EMG to acquire activity from the illio-psoas, extensor hallicus longus, extensor digitorum longus & other deep muscles muscle. We will also record individual limb loading & level of BWS during standing & stepping conditions. We may acquire continuous blood pressure with a finger cuff, breathing rate using an elastic band place loosely around their chest & temperature with 1-3 small sensors taped over their skin above & below their injury level. Locomotor Training Intervention. Individuals with SCI will participate in 80 sessions of weight bearing step-training (n=10) for approx 16 - 20 weeks (60-90 min/session, 3-5 sessions/wk) during which the individuals will be placed on the treadmill in an upright position & suspended by an overhead pulley in a harness. During stepping using BWST & manual assistance the maximum load will be used that avoids knee-buckling & trunk collapse. A trainer positioned behind the research participant will aid in pelvis & trunk stabilization, as well as weight shifting & hip rotation, & trainers positioned at each limb will provide manual assistance using a customized technique that facilitates knee extension during stance (by manually stimulating the patellar & Achilles' tendons) & knee flexion & toe clearance during swing (by manually stimulating the hamstrings & tibialis anterior tendons). Trainers provide assistance only when needed. Individuals will step at a normal walking speed for their height & age (0.89 m/s - 1.34 m/s) & at the maximum body weight allowed with minimal force needed by the trainers to assist during stance. BWS will be continuously reduced over the course of the 80 sessions as the individuals increase their ability to bear weight on the legs during stepping. Participants may also stand train in a stand training device, based on optimal parameters acquired during the initial phase of training. The participant might be asked to follow a supine &/or stand training home program (in a standing frame or similar device) once independence is achieved with the stimulation. The home program will only be used as a complement to the daily outpatient training sessions, & will be closely monitored by the research team. The research participants will have to demonstrate independence & safe use of the patient programmer in the lab prior to initiation of the home program. Parameters loaded in the patient programmers will only include those that have been used safely and result in supine movements or independent standing by the research participant in the laboratory setting. In addition, family members & caregivers will be trained on appropriate techniques to provided assistance as needed during home-based training. Independent standing & availability of caregivers to provided assistance in the home environment will be key factors when developing the home program. We will collect electromyography (EMG), joint angle, & footswitch data at 1000 Hz using a 24-channel hard-wired analog to digital board & a custom written Labview software acquisition program during stepping using BWST & manual assistance. EMG data will be sampled from 0.1 to 1 kHz & AC coupled into a differential amplifier. Following standard skin preparation, bipolar surface EMG electrodes with a fixed distance between the electrodes will be placed on the soleus, medial gastrocnemius, tibialis anterior, medial hamstrings, adductor, vastus lateralis, & rectus femoris bilaterally. Limb kinematics will be digitally acquired a passive marker high speed motion capture system. Individual limb loads will be measured with shoe-insole pressure sensors. Data will be processed & synchronized using Labview software customized by our laboratory. EMG data will be full wave rectified & filtered using a 4th order bandpass Butterworth filter (40 Hz - 500 Hz). Mean EMG represents the relative number & frequencies of the motor units recruited per burst. Integrated EMG assesses the total EMG activity generated per step. EMG mean & integrated amplitudes from each muscle will be compared before and after LT. Co-activation values of flexors and extensors will be calculated. The degree of coordination in the stepping-related oscillations of lower limb segments will be assessed through principal component analysis. Quantitative measurements and statistical testing have been described in detail in previous publications listed above. Heart rate will be monitored during training sessions and experiments.


Criteria:

Inclusion Criteria: - All research participants, irrespective of age or sex, will meet the following criteria: 1. stable medical condition without cardiopulmonary disease or dysautonomia that would contraindicate standing or stepping with BWST; 2. no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore, or urinary tract infection that might interfere with stand or step training; 3. no clinically significant depression or ongoing drug abuse; 4. no current anti-spasticity medication regimen; 5. non-progressive SCI above T10; 6. must not have received botox injections in the prior six months; 7. be unable to stand or step independently; 8. at least one-year post injury; and 9. must be at least 18 years of age. In addition, all subjects must satisfy each of the three conditions of the functional neurophysiological assessment described below. Functional Neurophysiological Assessment (FNPA). We will use FNPA to screen potential research participants based on specific neurophysiological inclusion criteria. Participants must have no volitional control of movement below the level of the lesion, but must retain some brain influence on spinal reflexes. Our target population, which will be identified by FNPA, cannot be identified reliable using traditional assessments: hence individual subjects may be classified widely as Class A, B, or C on the ASIA SCI scale. We will include only subjects who fulfill the following three requirements: 1. There is no descending volitional control of movement below the lesion 2. Segmental reflexes remain functional below the lesion 3. Brain influence on spinal reflexes is retained Exclusion Criteria: 1. Ventilatory dependent 2. painful musculoskeletal function, unhealed fracture, contracture, or pressure sore that might interfere with training; 3. clinically significant depression or ongoing drug abuse; 4. cardiovascular, respiratory, bladder or renal disease unrelated to SCI; 5. severe anemia (Hgb<8 g/dL) or hypovolemia; and 6. HIV or AIDS related illness.


NCT ID:

NCT02339233


Primary Contact:

Claudia Angeli, PhD
Phone: 502-582-8675
Email: locomotorresearch@kentuckyonehealth.org


Backup Contact:

N/A


Location Contact:

Louisville, Kentucky 40202
United States

Susan J Harkema, PhD
Phone: 502-581-7443
Email: locomotorresearch@kentuckyonehealth.org

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 23, 2017

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

If you would like to be contacted by the clinical trial representative please fill out the form below.