Paraparesis, Paraplegia, Spinal Cord Injuries
Conditions
Keywords
spinal cord injuries, paraplegia, postural balance, locomotor activity, exercise therapy, electromyography, transcranial magnetic stimulation, single pulse
Brief summary
Many people with spinal cord injury (SCI) retain at least some movement below their injury, but their muscles often have a 'mind of their own'. Typical exercise programs focus on keeping muscles strong and flexible, but don't usually focus on helping patients control their muscles. The investigators' exercise research study will compare two different programs with the specific goal of improving conscious control of patients' muscles below the injury. This study focuses on those with 'chronic' SCI - the injury occurred at least one year prior to enrolling. This is a single center study taking place in the Bronx, NY. The first phase of the study will be observational - the investigators will analyze which nerve connections might remain partially intact through the injury (even if the nerves aren't consciously controlled). Participants with all severity of SCI may participate in this first phase. The second phase of the study will involve people who retain at least slight ability to move their legs and the ability to move the arms against gravity. Each person will undergo two different exercise rehabilitation strategies: weight-supported treadmill training; and balance training combined with skilled arm or hand exercises. The investigators will compare the effects of these exercise programs on a variety of outcomes, including gait speed, balance, strength, and muscle activation in response to brain stimulation. The investigators hypothesize that participants with chronic SCI undergoing combined balance/arm/hand training will show improved outcomes when compared to traditional gait or balance training.
Interventions
DEVICERobotic body weight supported treadmill training
30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.
OTHERHarness-supported multimodal balance training
30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males or females age 21-65 years; * SCI duration \> 12 months; * SCI level C2-T12; * All SCI severity eligible for baseline testing; * For exercise protocol, must have severity of Grade C or D on American Spinal Injury Association (ASIA) Impairment Scale, or volitional strength of at least 1/5 in two or more key lower extremity muscles, as well as at least 3/5 in both shoulder and elbow muscles; * Able to tolerate upright position with support; * Morphologically capable of fitting a weight-support harness and robotic treadmill system; * Ability to give informed consent.
Exclusion criteria
* Unsuitable cognitive capacity as judged by the study physician; * Diagnosis of neurological injury other than SCI, such as stroke, traumatic brain injury, or other neurological condition that the study physician considers to be exclusionary; * Multiple spinal cord lesions; * History of frequent autonomic dysreflexia; * History of seizures; * Use of medications that significantly lower seizure threshold, such as anti-psychotics, tricyclic antidepressants, amphetamines, and bupropion; * History of implanted brain/spine/nerve stimulators, aneurysm clips, or cardiac pacemaker/defibrillator; * Deep vein thrombosis in lower extremities of less than 6 months duration; * Pregnancy; * (Interventional phase only): Lack of detectable tibialis anterior motor evoked potential (MEP) at baseline even with active facilitation; * (Interventional phase only): Pressure ulcers greater than stage 1 severity on the foot, ankle, knee and/or pelvic girdle; * (Interventional phase only): Bone mineral density of the hip (proximal femur) T-score \<3.5 standard deviations from age- and gender-matched normative data; * (Interventional phase only): Any spasticity, contractures, or heterotopic ossification that result in inadequate range of motion of the shoulder, elbow, wrist, fingers, hip, knee, or ankle joints in the judgment of the study physician; * (Interventional phase only): Inability to cooperate with instructions or unwilling to commit to daily training sessions for 3-4 days per week over 12-16 weeks; * (Interventional phase only): A diagnosis of coronary artery disease that precludes moderate to intense exercise.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Motor Evoked Potential (MEP) Amplitude in the Tibialis Anterior Muscle at the End of Training. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in motor evoked potential area in the tibialis anterior muscle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Berg Balance Scale Sitting With Back Unsupported Score. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in Berg sitting unsupported subscore. Range 0-4, higher better. |
| Change in Leg Spasticity on Modified Ashworth Scale | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in modified Ashworth Scale. 0-4 score, lower is better. |
| Change in Gait Speed on 10-meter Walk Test. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in gait speed during 10-meter walk test. |
| Change From Baseline in Walking Index for Spinal Cord Injury II (WISCI II) Scale. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in WISCI II score. Scores range 0-20, higher is better. |
| Change From Baseline in ISNCSCI Lower Extremity Motor Score. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in lower extremity motor score derived from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Range of scores 0-50, higher is better. |
| Change in Subjective Pain as Determined by McGill Pain Questionnaire (Short Form). | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in McGill Pain Questionnaire (Subjective Domain). Total scale 0-45, lower is better. |
| Change From Baseline in Endpoint Excursion and Directional Control Parameters Achieved During Seated Limits of Stability Testing. | Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Seated posturography performed using the Limits of Stability module of the Smart EquiTest apparatus (Neurocom) while seated. Directional Control measure. |
| Change From Baseline in Soleus H-reflex Facilitation. | Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in soleus H-reflex facilitation by transcranial magnetic stimulation (TMS). Short-interval 0-20ms. |
| Changes From Baseline in Survey: Spinal Cord Injury - Spasticity Evaluation Tool (SCI-SET) | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in SCI-SET score. Range of scores -105 to +105. Higher is better. |
| Change From Baseline in Total Number of Steps Taken by Both Feet During Seated 10-second Step Test. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | Change between baseline and Evaluation #2 in steps taken during 10-second step test. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Multimodal Then Treadmill Training Participants will undergo harness-supported multimodal balance training exercises while simultaneously performing skilled hand exercises. Following a washout period of at least 6 weeks, Participants will undergo body weight supported treadmill training using the Lokomat apparatus.
Multimodal training: 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.
Robotic body weight supported treadmill training: 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks. | 10 |
| Treadmill Then Multimodal Training Robotic body weight supported treadmill training will be applied using the Lokomat apparatus. Following a washout period of at least 6 weeks, Participants will undergo harness-supported balance training exercises while simultaneously performing skilled hand exercises.
Multimodal training: 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.
Robotic body weight supported treadmill training: 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks. | 11 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insufficient protocol compliance | 2 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Multimodal Then Treadmill Training | Treadmill Then Multimodal Training | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment United States | 10 Participants | 11 Participants | 21 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 10 | 3 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Change in Motor Evoked Potential (MEP) Amplitude in the Tibialis Anterior Muscle at the End of Training.
Change between baseline and Evaluation #2 in motor evoked potential area in the tibialis anterior muscle.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Only two participants in the study had consistent MEPs at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Multimodal Training | Change in Motor Evoked Potential (MEP) Amplitude in the Tibialis Anterior Muscle at the End of Training. | -1.75 Amplitude percentage of Mmax |
| Treadmill Training | Change in Motor Evoked Potential (MEP) Amplitude in the Tibialis Anterior Muscle at the End of Training. | -2.01 Amplitude percentage of Mmax |
Secondary
Change From Baseline in Berg Balance Scale Sitting With Back Unsupported Score.
Change between baseline and Evaluation #2 in Berg sitting unsupported subscore. Range 0-4, higher better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change From Baseline in Berg Balance Scale Sitting With Back Unsupported Score. | 0.10 units on a scale | Standard Deviation 0.32 |
| Treadmill Training | Change From Baseline in Berg Balance Scale Sitting With Back Unsupported Score. | 0.00 units on a scale | Standard Deviation 0 |
Secondary
Change From Baseline in Endpoint Excursion and Directional Control Parameters Achieved During Seated Limits of Stability Testing.
Seated posturography performed using the Limits of Stability module of the Smart EquiTest apparatus (Neurocom) while seated. Directional Control measure.
Time frame: Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change From Baseline in Endpoint Excursion and Directional Control Parameters Achieved During Seated Limits of Stability Testing. | 1.93 Percentage of perfect path to target | Standard Error 3.42 |
| Treadmill Training | Change From Baseline in Endpoint Excursion and Directional Control Parameters Achieved During Seated Limits of Stability Testing. | 8.42 Percentage of perfect path to target | Standard Error 4.02 |
Secondary
Change From Baseline in ISNCSCI Lower Extremity Motor Score.
Change between baseline and Evaluation #2 in lower extremity motor score derived from the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Range of scores 0-50, higher is better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: One subject in multimodal group failed to appear for post-intervention testing for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change From Baseline in ISNCSCI Lower Extremity Motor Score. | 0.11 units on a scale | Standard Deviation 4.81 |
| Treadmill Training | Change From Baseline in ISNCSCI Lower Extremity Motor Score. | -0.30 units on a scale | Standard Deviation 4.32 |
Secondary
Change From Baseline in Soleus H-reflex Facilitation.
Change between baseline and Evaluation #2 in soleus H-reflex facilitation by transcranial magnetic stimulation (TMS). Short-interval 0-20ms.
Time frame: Time Frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing, and due to lack of soleus H-reflex in several subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change From Baseline in Soleus H-reflex Facilitation. | 6.63 percentage of control reflex size | Standard Error 6.25 |
| Treadmill Training | Change From Baseline in Soleus H-reflex Facilitation. | -5.20 percentage of control reflex size | Standard Error 3.35 |
Secondary
Change From Baseline in Total Number of Steps Taken by Both Feet During Seated 10-second Step Test.
Change between baseline and Evaluation #2 in steps taken during 10-second step test.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Low number of participants able to perform seated steps at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change From Baseline in Total Number of Steps Taken by Both Feet During Seated 10-second Step Test. | 2.83 steps | Standard Error 1.14 |
| Treadmill Training | Change From Baseline in Total Number of Steps Taken by Both Feet During Seated 10-second Step Test. | -1.08 steps | Standard Error 1.03 |
Secondary
Change From Baseline in Walking Index for Spinal Cord Injury II (WISCI II) Scale.
Change between baseline and Evaluation #2 in WISCI II score. Scores range 0-20, higher is better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Insufficient number of participants able to walk at baseline. Measure not recorded by Investigating team.
Secondary
Change in Gait Speed on 10-meter Walk Test.
Change between baseline and Evaluation #2 in gait speed during 10-meter walk test.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Insufficient number of participants able to walk at baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change in Gait Speed on 10-meter Walk Test. | .04 meters per second | Standard Deviation 0 |
| Treadmill Training | Change in Gait Speed on 10-meter Walk Test. | 0.12 meters per second | Standard Deviation 0.132 |
Secondary
Change in Leg Spasticity on Modified Ashworth Scale
Change between baseline and Evaluation #2 in modified Ashworth Scale. 0-4 score, lower is better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing, and due to incomplete outcome assessment by Investigating team.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change in Leg Spasticity on Modified Ashworth Scale | 0.13 units on a scale | Standard Deviation 0.25 |
| Treadmill Training | Change in Leg Spasticity on Modified Ashworth Scale | -0.39 units on a scale | Standard Deviation 0.89 |
Secondary
Change in Subjective Pain as Determined by McGill Pain Questionnaire (Short Form).
Change between baseline and Evaluation #2 in McGill Pain Questionnaire (Subjective Domain). Total scale 0-45, lower is better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing, and due to incomplete outcome assessment by Investigating team.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Change in Subjective Pain as Determined by McGill Pain Questionnaire (Short Form). | 0.89 units on a scale | Standard Deviation 2.76 |
| Treadmill Training | Change in Subjective Pain as Determined by McGill Pain Questionnaire (Short Form). | -0.93 units on a scale | Standard Deviation 3 |
Secondary
Changes From Baseline in Survey: Spinal Cord Injury - Spasticity Evaluation Tool (SCI-SET)
Change between baseline and Evaluation #2 in SCI-SET score. Range of scores -105 to +105. Higher is better.
Time frame: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months)
Population: Incomplete analysis due to dropouts before post-testing, and due to incomplete outcome assessment by Investigating team.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Multimodal Training | Changes From Baseline in Survey: Spinal Cord Injury - Spasticity Evaluation Tool (SCI-SET) | 2.14 units on a scale | Standard Deviation 11.44 |
| Treadmill Training | Changes From Baseline in Survey: Spinal Cord Injury - Spasticity Evaluation Tool (SCI-SET) | -0.67 units on a scale | Standard Deviation 0.82 |