Multimodal Exercises to Improve Leg Function After Spinal Cord Injury

Study Overview
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Brief Summary
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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.

Official Title
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A Hebbian Approach to Regaining Control of Spared Circuits in Spinal Cord Injury

Conditions
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Spinal Cord Injuries, Paraplegia, Paraparesis

Intervention / Treatment
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* Device: Robotic body weight supported treadmill training
* Other: Harness-supported multimodal balance training


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multimodal then Treadmill training<br>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. | Device: Robotic body weight supported treadmill training<br>* 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.<br>* Other names: Lokomat;Other: Harness-supported multimodal balance training<br>* 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.<br>* Other names: balance exercises, skilled hand exercises;|
| Active Comparator: Treadmill then Multimodal training<br>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. | Device: Robotic body weight supported treadmill training<br>* 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.<br>* Other names: Lokomat;Other: Harness-supported multimodal balance training<br>* 30-minute sessions will be conducted 3-4 times per week for a total of 48 sessions over 12 to 16 weeks.<br>* Other names: balance exercises, skilled hand exercises;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| Change in Leg Spasticity on Modified Ashworth Scale | Change between baseline and Evaluation #2 in modified Ashworth Scale. 0-4 score, lower is better. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| Change in Gait Speed on 10-meter Walk Test. | Change between baseline and Evaluation #2 in gait speed during 10-meter walk test. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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: Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 
| 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. | Eval #1 at baseline; Eval #2 at end of training (48 sessions, average 3-4 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spinal cord injuries, paraplegia, postural balance, locomotor activity, exercise therapy, electromyography, transcranial magnetic stimulation, single pulse