Spinal Cord Injury
Conditions
Keywords
Epidural Stimulation
Brief summary
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.
Detailed description
Participants will be screened for eligibility and then participate in pre-training motor, bladder and cardiovascular experiments, followed by 80 sessions of locomotor training. Participants will repeat experiments after the 80 training sessions to quantify that no motor pattern changes are achievable with locomotor training alone and will be evaluated for appropriate candidacy for surgery and epidural stimulation. Participants will be surgically implanted with an epidural stimulator and experiments will be conducted with and without stimulation. Investigators will identify appropriate stimulation parameters for inducing stepping and standing in combination with manual assistance using body weight support on a treadmill and/or overground. Participants will undergo 80-200 training sessions of locomotor training with epidural stimulation. Experiments will be repeated mid and post-training interventions.
Interventions
DEVICEStanding and Stepping with spinal cord Epidural Stimulation
Standing and Stepping with support from trainers as needed, overground or in a harness with body weight support on a treadmill. Epidural stimulation with specific configurations will be administered to generate standing and stepping.
Sponsors
University of California, Los Angeles
Christopher Reeve Paralysis Foundation
Kessler Foundation
The Leona M. and Harry B. Helmsley Charitable Trust
National Institute for Biomedical Imaging and Bioengineering (NIBIB)
University of Louisville
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* All research participants, irrespective of age or sex, will meet the following criteria: * stable medical condition without cardiopulmonary disease or dysautonomia that would contraindicate standing or stepping with BWST; * no painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore, or urinary tract infection that might interfere with stand or step training; * no clinically significant depression or ongoing drug abuse; * no current anti-spasticity medication regimen; * non-progressive SCI above T10; * must not have received botox injections in the prior six months; * be unable to stand or step independently; * at least one-year post injury; and * 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: * There is no descending volitional control of movement below the lesion * Segmental reflexes remain functional below the lesion * Brain influence on spinal reflexes is retained
Exclusion criteria
* Ventilatory dependent * painful musculoskeletal function, unhealed fracture, contracture, or pressure sore that might interfere with training; * clinically significant depression or ongoing drug abuse; * cardiovascular, respiratory, bladder or renal disease unrelated to SCI; * severe anemia (Hgb\<8 g/dL) or hypovolemia; and * HIV or AIDS related illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year) | Baseline, 160 sessions (1 year) | We will measure the amount of time individuals are able to stand without manual assistance (independently) throughout a 10 min bout |
| Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year) | Baseline, 160 session (1 year) | We will measure the number of steps individuals are able to take without manual assistance (independently) throughout a 6 min stepping bout |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year) | Baseline, 160 sessions (1 year) | We will measure the ability of the individuals to perform consecutive hip flexion repetitions with stimulation during a 1 minute period |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epidural Stimulator Eligible participants will be implanted with 16-electrode epidural array in the T11-L1 area of the spinal cord
Standing and Stepping with spinal cord Epidural Stimulation: Standing and Stepping with support from trainers as needed, overground or in a harness with body weight support on a treadmill. Epidural stimulation with specific configurations will be administered to generate standing and stepping. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Epidural Stimulator | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 8 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 7 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 5 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
Primary
Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year)
We will measure the amount of time individuals are able to stand without manual assistance (independently) throughout a 10 min bout
Time frame: Baseline, 160 sessions (1 year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epidural Stimulator | Change From Baseline of Lower Extremity Independence Time During 10 Min Standing Bout After 160 Sessions (1 Year) | 40.6 minutes | Standard Deviation 30.2 |
Primary
Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year)
We will measure the number of steps individuals are able to take without manual assistance (independently) throughout a 6 min stepping bout
Time frame: Baseline, 160 session (1 year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epidural Stimulator | Change From Baseline of Stepping Independence Time During 6 Min Stepping Bout After 160 Sessions (1 Year) | 197.13 steps | Standard Deviation 421.89 |
Secondary
Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year)
We will measure the ability of the individuals to perform consecutive hip flexion repetitions with stimulation during a 1 minute period
Time frame: Baseline, 160 sessions (1 year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epidural Stimulator | Change From Baseline of Number of Consecutive Hip Flexion Repetitions Performed Within One Minute After 160 Sessions (1 Year) | 14.25 Repetitions | Standard Deviation 9.8 |