Paraplegia, Spastic, Paraplegia, Spinal, Spinal Cord Injuries, Tetraplegia/Tetraparesis
Conditions
Keywords
Locomotor Training, Transcutaneous Spinal Cord Stimulation, Lokomat, Peripheral Nerve Stimulation, H-Reflex, Spinal Neural Circuits, Neuroplasticity, Recovery
Brief summary
Locomotor training is often used with the aim to improve corticospinal function and walking ability in individuals with Spinal Cord Injury. Excitingly, the benefits of locomotor training may be augmented by noninvasive electrical stimulation of the spinal cord and enhance motor recovery at SCI. This study will compare the effects of priming locomotor training with high-frequency noninvasive thoracolumbar spinal stimulation. In people with motor-incomplete SCI, a series of clinical and electrical tests of brain and spinal cord function will be performed before and after 40 sessions of locomotor training where spinal stimulation is delivered immediately before either lying down or during standing.
Detailed description
Spinal cord injury (SCI) greatly impairs standing and walking ability, which severely compromises daily living activities. While these deficits are partially improved by locomotor training, even after multiple training sessions, abnormal muscle activity and coordination still persist. Thus, locomotor training alone cannot fully optimize the neuronal plasticity required to strengthen the synapses connecting the brain, spinal cord, and local circuits. As such, treatment interventions that effectively promote neuromodulation of spinal locomotor networks and strengthen neural connectivity of the injured human spinal cord in combination with physical rehabilitation are greatly needed. It is proposed that transcutaneous spinal cord (transspinal) stimulation as a method to synergistically 'prime' the nervous system to better respond to locomotor training. Transspinal stimulation alters motoneuron excitability over multiple spinal segments, a pre-requisite for functioning descending and local inputs. Importantly, whether concurrent treatment with transspinal stimulation and locomotor training maximizes motor recovery after SCI is unknown. The goal of this clinical trial is to use high frequency (30 Hz) transspinal stimulation to prime locomotor training and ultimately improve standing, walking, and overall function in individuals with chronic incomplete SCI (iSCI). Forty-five individuals with iSCI will undergo 40 sessions of body weight-supported step training primed with high-frequency transspinal stimulation. Participants will be randomized to receive transspinal stimulation during standing (real or sham) or while supine (real). Aim 1 evaluates how priming locomotor training with high-frequency transspinal stimulation in SCI alters corticomotoneuronal connectivity strength, as indicated by motor evoked potentials recorded from the legs. Aim 2 evaluates how priming locomotor training with high-frequency transspinal stimulation in iSCI affects reorganization and appropriate engagement of spinal neuronal circuits. Finally, Aim 3 evaluates activity-based motor function, ability to stand and walk, and quality of life. These results will support the notion that tonic high-frequency transspinal stimulation strengthens corticomotoneuronal connectivity and improves spinal circuit organization through posture-dependent corticospinal neuroplasticity. It is anticipated that the information gained from this mechanistic clinical trial will greatly impact clinical practice. This is because in real-world clinical settings, noninvasive transspinal stimulation can be more easily and widely implemented than invasive epidural stimulation.
Interventions
COMBINATION_PRODUCTStanding transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation during standing followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
COMBINATION_PRODUCTLying transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of non-invasive high frequency (e.g. 30 Hz) transcutaneous transspinal stimulation while lying supine on a therapy table followed by 30 minutes of assisted stepping robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
OTHERStanding sham transspinal stimulation followed by robotic gait training
Fifteen people with spinal cord injury will receive 40 daily sessions of 30 minutes of sham transspinal stimulation during standing at an intensity where sensation is absent followed by 30 minutes of robotic gait training. Before and after training standardized clinical and neurophysiological tests will be used to assess recovery of sensorimotor function.
Sponsors
City University of New York
Bronx Veterans Medical Research Foundation, Inc
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a mechanistic randomized clinical trial. We will enroll 45 individuals with SCI. We will use blocked randomization into three groups with a block size of nine, with stratification according to severity of SCI (ambulatory with assistive device, or not ambulatory).1 We will check after completion of intervention by all subjects in each group whether the groups are balanced or not regarding baseline motor function and perform tests of association accordingly.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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. * Male or female, age 18-70 years old. * In good general health as evidenced by medical history. * Diagnosed with motor incomplete SCI (AIS 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. * Presence of tendon reflexes to be able to elicit the soleus H-reflex. * Absent permanent ankle joint contractures that prevent passive or active ankle movement because corticospinal and spinal excitability is based on the ankle angle. The ankle straps of the Lokomat require also 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. * Significant neuropathies of the peripheral nervous system. * Significant degenerative neurological disorders of the spine or spinal cord. * AIS A or B. * 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, pacemaker, implanted infusion device, and/or implanted stimulators of any type and purpose will be excluded to avoid their malfunction due to stimulation. * People with history of seizures. * Medical conditions that increase the possibility of seizures. * Medications that may change the seizure threshold.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasticity of Spinal Neuronal Networks - Homosynaptic Depression | 4-6 months | Soleus H-reflexes following posterior tibial nerve stimulation with a 1-ms monophasic pulse were recorded with subjects seated and stimuli delivered every 1 s (1.0 Hz), 3 s (0.33 Hz), 5 s (0.2 Hz), 8 s (0.125 Hz), and 10s (0.1 Hz). Results for each interval vs 0.1 Hz shown. |
| Plasticity of Spinal Neuronal Networks - Presynaptic Inhibition | 4-6 months | Presynaptic inhibition was assessed with a conditioning pulse train of 4 pulses with 9 ms duration, delivered to the CPN at the C-T intervals of 20, 60, or 100 ms. These C-T intervals were selected because the reflex inhibition produced at the intermediate C-T intervals is predominantly presynaptic. The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively. Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged. Results are listed for each C-T interval, pre- and post-intervention. |
| Plasticity of Spinal Neuronal Networks - Reciprocal Inhigition | 4-6 months | To assess restoration of reciprocal Ia inhibition, soleus H-reflexes were recorded following common peroneal nerve (CPN) stimulation at short conditioning-test (C-T) intervals of 0, 1, 2, 3, and 4 ms. The stimulus to the CPN was delivered at 1.27 ± 0.12 (21.8 ± 10.1 mA) and 1.4 ± 0.28 (21.8 ± 10.1 mA) TA motor threshold before and after treatment, respectively. Control and conditioned soleus H-reflexes were randomly recorded across the C-T intervals tested, and 15 H-reflexes were recorded at each C-T interval. For each participant at each timepoint, amplitudes across the 15 H-reflexes per C-T interval were averaged. Results are listed for each C-T interval, pre- and post-intervention. |
| Plasticity of Corticospinal Networks | 4-6 months | Neurophysiological measurements assessing changes in corticospinal excitability from the interventions by recording responses to single-pulse transcranial magnetic stimulation (TMS) at rest and during robotic-assisted stepping. The tibialis anterior resting motor threshold (RMT) was established and corresponded to the lowest TMS maximal stimulator output that induced reproducible evoked potentials of at least \~50 µV in 4 out of 5 consecutive single TMS pulses. RMTs (percentage of maximal stimulator output) are shown pre- and post-intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Autonomic Function | 4-6 months | SCIM III Bladder and Bowel management subscores Bladder subscore rated 0-15 (higher means better bladder function). Bowel subscore rated 0-10 (higher means better bowel function). |
| Ambulatory Function | 4-6 months | Change in 10-meter timed test (seconds required to complete 10-meter walk) between baseline and post-intervention. Fewer seconds means faster (better) gait. |
| Balance | 4-6 months | Changes in Berg Balance Scale score between baseline and post-intervention. Scale scores between 0 and 56. Higher scores mean better balance. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMaria Knikou, PT, PhD
Research Foundation of the City University of New York
PRINCIPAL_INVESTIGATORNoam Y. Harel, MD, PhD
Bronx Veterans Medical Research Foundation
Participant flow
Recruitment details
Participants with SCI were recruited from various sources: Each site's existing databases of past research participants; people with SCI seen clinically at the James J. Peters VA Medical Center and Mount Sinai Medical Center; via flyers and webpage notices; and through various tabling events at local expositions and gyms that cater to people with SCI.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44.5 Years STANDARD_DEVIATION 17.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 1 / 4 | 3 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 5 | 0 / 5 |
Outcome results
None listed