Arm and Leg Cycling for Accelerated Recovery From SCI

Study Overview
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Brief Summary
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The purpose of this study is to examine the ability of simultaneous motorized upper and lower extremity cycling training to regulate spinal movement patterns in order to potentially restore functional abilities (i.e., walking) in individuals with an incomplete spinal cord injury. The researchers hypothesize there will be improved walking function following motorized cycling.

Detailed Description
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Spinal cord injury (SCI) occurs at an annual rate of 50-60 per million in North America. Paralysis is also accompanied by drastic changes in independence and quality of life. SCI occurs mostly among younger individuals, half in people 16-30 years of age. Two-thirds of all SCIs are incomplete (iSCI), with some preserved neural connections relaying information to and from the brain. People with iSCI benefit most from improvements in walking. In addition to increasing independence, walking helps persons with iSCI remain active, with a variety of beneficial health-related outcomes. Therapy that can significantly increase sensorimotor function to these individuals living with iSCI for multiple decades would be hugely significant. Currently, the most common strategies for restoring walking after an iSCI are manually intensive, including over ground walking with weight and balance support provided by multiple therapists, or with the use of expensive robotic support with controversial outcomes. Thus, the overarching goal of this proposal is to investigate if a non-specific gait rehabilitation paradigm based on motor-assisted arms and legs cycling in AIS C and D iSCI individuals generalizes to improvements in walking that outperform conventional gait specific training (Specific Aim 1). The researchers will also investigate biomechanical and motor coordination changes and adaptations tied to these functional improvements (Specific Aim 2), and the neural mechanisms that explain functional improvements and their retention over time (Specific Aim 3). Specifically, in Specific Aim 1 the researchers will investigate the clinically-relevant gait improvements afforded by the cycling intervention. In Specific Aim 2 the researchers will focus on studying the detailed biomechanical basis for the gait improvements. In Specific Aim 3 the researchers will investigate the neuroplastic mechanisms underlying the gait improvements. For these Aims, the researchers will measure the walking gains with a battery of standard clinical tests focused on motor function, sensation, balance and spasticity (Specific Aim 1). The researchers will use motion tracking, force plates, and EMG measurement to monitor the kinematics and kinetics of gait, the neuromuscular coordination, and oxygen consumption as a measure of these energetics of walking (Specific Aim 2). In addition, the researchers will conduct a battery of physiological tests at 3-week intervals intended to detect changes in the strength of descending and ascending spinal pathways (Specific Aim 3).

Official Title
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Upper and Lower Extremity Cycling in Incomplete Spinal Cord Injury Individuals to Promote Limb Recovery

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Motor-assisted arms and legs cycling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic SCI T11 and above (upper motorneuron lesion) Incomplete paraplegia or tetraplegia (Classified as AIS C or D) Age range 18-75 years old, inclusive At least 1 year post- injury Independent ambulator (with normal assistive devices or bracing) for at least 10 meters (30 feet) Walking speed <0.8 m/s (2.62 ft/s) (or per researcher discretion) Bilateral arm strength to arm cycle at least 15 minutes without assistance (or per researcher discretion) Exclusion Criteria: Traumatic SCI T12 and below (or lacking upper motorneuron injury) Complete paraplegia or tetraplegia (classified as AIS A) AIS B incomplete paraplegia or tetraplegia Presence of progressive neurologic disease Unable to give informed consent to participate in the study Significant other disease (ex: cardiological or heart disease, renal, hepatic, malignant tumors, mental or psychiatric disorders) that would prevent participants from fully engaging in study procedures MRI contraindications: Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps Metal in the body (rods, plates, screws, shrapnel, dentures, metal IUD, etc) Surgical clips in the head or previous neurosurgery Cochlear implants Prosthetic heart valves Claustrophobia Tremor TMS contraindications Epilepsy or any other type of seizure history Medications that increase the risk of seizures Non-prescribed drug or marijuana use Depression, antidepressant medications, or antipsychotic medications Pregnancy Prisoners

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: The participants will complete 60min of active cycling training paradigm, 5 times a week, for 12 weeks. The cycling ergometer will be used to provide motorized assistance during simultaneous arms and legs cycling to the participant while they are seated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCI subject<br>Subject with SCI | Device: Motor-assisted arms and legs cycling<br>* The participants will complete 60min of active cycling training paradigm, 5 times a week, for 12 weeks. The cycling ergometer will be used to provide motorized assistance during simultaneous arms and legs cycling to the participant while they are seated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 10-meter walking test (10MWT) | The 10-meter walking test (10MWT) is a physical function test measuring the total time to ambulate 10 meters in order to calculate walking speed in meters per second. A shorter time indicates a better walking speed. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in 6-minute walking test (6MWT) | The 6-minute walking test (6MWT) is a physical function test measuring the total distance walked in a span of six minutes will be assessed. A longer distance indicates a better walking distance. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in motor and sensory scores (ASIA) | The American Spinal Injury Association Impairment Scale (AISA) is a standardized neurological examination used to assess the sensory and motor levels which were affected by the spinal cord injury. A clinician will assess sensory and strength in both upper and lower extremities to provide both a neurologic level of injury and classification level. The five classification levels, ranging from complete loss of neural function in the affected area (Grade A) to completely normal (Grade E). A score closer to Grade E is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in balance with the Berg balance scale (BBS) | Change in static and dynamic sitting and standing balance will be assessed using the Berg balance scale (BBS). Items are scored from zero to four. A higher score indicates better balance and decreased fall risk. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in walking ability with the WISCI | The Walking Index for Spinal Cord Injury (WISCI) assesses the ability of a person to walk after spinal cord injury. It consists of a rank ordering at the impairment level from most severe (0) to least severe (20) based on the amount of physical assistance required and use of assistive devices and/or braces while walking a 10-meter distance. A higher score indicates better walking ability. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in Modified Ashworth Scale (MAS) | The Modified Ashworth Scale (MAS) is a physical function test measuring spasticity on a 6-point ordinal scale. A score of 0 on the scale indicates no increase in tone while a score of 4 indicates rigidity. Tone is scored by passively moving the individual's limb and assessing the amount of resistance to movement felt by the examiner. A lower score is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in muscle testing or strength | Physical function test measuring strength of the muscle of interest. A muscle is isolated, and gradual external force is applied at a right angle to the muscle's long axis. Each muscle is scored on a graded scale of weak (score of 0) to strong (score of 5) based on the participant's ability to resist the external force. The test is first completed for muscles on the unimpaired side to determine normal strength before being repeated on the impaired side. Weaker participants may be tested while lying prone (gravity eliminated). A higher score value indicates higher strength and improvement. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Changes in EMG activation patterns | Electrodes will record muscle activity from the main leg muscles (e.g., soleus (SOL), tibialis anterior (TA), quadriceps (QS), hamstrings (HS)) during walking. Features closer to that of a healthy individual is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Changes in interlimb (upper-lower limb) modulation | This will be assessed by measuring changes in the magnitude and pattern of H-reflex suppression in the soleus (ankle extensor) of the leg during arm cycling. Features closer to that of a healthy individual is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Changes in the strength of cortico-spinal connectivity | This will be measured using transcranial magnetic stimulation (TMS) of the motor cortex known to produce a motor evoked potential (MEP) in the main muscles of the leg, and peak-to-peak amplitude of the MEP and recruitment curves of MEP amplitude as a function of TMS strength will be calculated and constructed. Recruitment curves closer to that of a healthy individual is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Changes in strength of periphery and somatosensory cortex | This will be measured using cutaneous electrodes on the arm and leg skin surface and recording the somatosensory evoked potentials (SEPs) over the primary somatosensory cortex using electroencephalography (EEG) electrodes; peak-to-peak amplitude of the SEP and recruitment curves of SEP amplitude as a function of stimulus strength will be calculated and constructed. Recruitment curves closer to that of a healthy individual is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in stride variability. | Stride variability is the ratio between the standard-deviation and mean of stride time, expressed as percentage. Decreased variability indicates a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in cadence. | Cadence is the total number of steps taken within a given time period; often expressed per minute. Typically a higher number of steps is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in step length. | Step length is the distance between the point of initial contact of one foot and the point of initial contact of the opposite foot. Typically a longer step length is a better outcome, ideally with equal measurements between left and right limbs. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in stride length. | Stride length is the distance between successive points of initial contact of the same foot. Right and left stride lengths are normally equal. Typically a longer stride length is a better outcome, ideally with equal measurements between left and right limbs. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 
| Change in stance time. | Stance time is the amount of time that passes during the stance phase of one extremity in a gait cycle. It includes single support and double support. Equal stance time between limbs is a better outcome. | Changes across baseline, after 3 weeks of training, after 6 weeks of training, after 9 weeks of training, after 12 weeks of training, and 6 months after completing training. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Rehabilitation, Cycling