Gait Recovery in Patients After Acute Ischemic Stroke

Study Overview
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Brief Summary
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More than 80% of ischemic stroke (IS) patients have some walking disability, which restricts their independence in the activities of daily living. Physical therapy (PT) significantly contributes to gait recovery in patients after IS. However, it remains unclear, what type of gait training is more effective and which factors may have impact on gait recovery. Two hundred fifty IS patients will be enrolled to undergo a 2-week intensive inpatient rehabilitation including randomly assigned robot-assisted treadmill gait training (RTGT) or therapist-assisted treadmill gait training (TTGT). A detailed clinical and laboratory assessment of gait quality, as well as the degree of neurological impairment, quality of life, cognition and depression will be performed in all patients during the study. We hypothesize that these variables may also affect gait recovery in patients after IS. In a randomly selected 60 enrolled patients, a multi-modal magnetic resonance imaging (MRI), including functional MRI, will be performed to assess neural correlates and additional predictors of gait recovery.

Detailed Description
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One hundred twenty consecutive first ever ischemic stroke patients classified as dependent walkers (Functional Ambulatory Category interval <1,3>) will be enrolled in the randomized blinded single center prospective clinical trial GAITFAST with a randomization either for robot-assisted treadmill gait training (RGT) or therapist-assisted treadmill gait training (TTGT) after acute phase (5-10 days after stroke onset). All enrolled patients will undergo a 2-week intensive inpatient rehabilitation including randomly assigned TTGT or RTGT followed with clinical visits (at the beginning of inpatient rehabilitation, at discharge, and three and six months after enrollment in the study). Each clinical visit will include detailed clinical functional assessments, assessment of spatiotemporal and kinetic gait parameters, assessment of neurological impairment, assessment of quality of life, cognition and depression. In 60 randomly selected enrolled IS patients, a repeated multi-modal magnetic resonance imaging (MRI) including functional MRI (fMRI) will be performed during the study follow-up to identify brain structures with possible impact on gait recovery.

Official Title
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GAIT Recovery in Patients aFter Acute Ischemic STroke: A Randomized Comparison of Robot-assisted and Therapist-assisted Gait Training on a Treadmill.

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Other: Robot-assisted treadmill gait training (RTGT)
* Other: Therapist-assisted treadmill gait training (TTGT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ischemic stroke detected on magnetic resonance imaging (MRI) with NIHSS score 1-12 points at the time of enrolment Lower limb movement impairment with a score of at least 1 point on the NIH Stroke Scale (NIHSS) at the time of enrolment Dependency in walking according to Functional Ambulatory Category (FAC) with score interval <1,3> (supervision or assistance, or both, must be given in performing walking) Exclusion Criteria: Previous history of any stroke, either ischemic or hemorrhagic Other diseases modifying or limiting walking ability, currently receiving rehabilitation or participation in another study Significant/symptomatic ischemic heart disease or significant/symptomatic peripheral arterial disease Obesity (BMI ≥ 40), or weight higher than 110 kg (weight limit for the robot-assisted gait training) Sensory aphasia with the inability to understand having been verified by a certified speech therapist. Moderate or severe depression present at the time of enrolment assessed using the Beck scale, with a score above 10. Known cognitive impairment Previous disability or dependence in the daily activities assessed using the modified Rankin Scale with a score of 3 and more points Currently receiving dialysis Diagnosed and/or receiving treatment for cancer Presence of other orthopedic or neurological conditions affecting the lower extremities For fMRI: Pregnancy; electronic implants, including cochlear implant, pacemaker, neurostimulator; incompatible metallic implants, including aneurysm clip; metallic intraocular foreign body; large tattoos; unremovable piercing; body weight over 150 kg; known claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Interventional Model Description: All participants will be randomly assigned to two parallel intervention groups for the duration of study. Thirty patients from each intervention group will be randomized to multimodal MRI of brain.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Robot-assisted treadmill gait training (RTGT)<br>Locomotor training guided by the robotic device (Lokomat Hocoma) according to a pre-programmed gait pattern with the help of robot-driven exoskeleton orthoses. The process of gait training is automated and controlled by a computer under supervision of a physiotherapist. | Other: Robot-assisted treadmill gait training (RTGT)<br>* Locomotor training guided by the robotic device (Lokomat Hocoma) according to a pre-programmed gait pattern with the help of robot-driven exoskeleton orthoses. The process of gait training is automated and controlled by a computer under supervision of a physiotherapist.<br>|
| Active Comparator: Therapist-assisted treadmill gait training (TTGT)<br>Locomotor training via a repetitive execution of walking movements manually guided by a physiotherapist during treadmill gait training. | Other: Therapist-assisted treadmill gait training (TTGT)<br>* Locomotor training via a repetitive execution of walking movements manually guided by a physiotherapist during treadmill gait training.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gait speed during overground walking | Gait speed will be measured using the 10 Meters Walking Test (performance measure used to assess walking speed in meters per second over a short distance). The subject will be asked to walk for a distance of 10 meters at his/her comfortable speed. The time will be measured for the distance of the middle six meters, which will allow walk acceleration and deceleration. Each patient will perform two trials with a calculation of mean time value. If physical assistance of another person (to prevent a fall or collapsing) is needed for a patient to complete the test, the level of assistance provided will be documented. Usage of any assistive device and/or bracing (that patients are currently using for walking and are needed to complete the test) will be also documented. | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in National Institute of Health Stroke Scale (NIHSS) | NIHSS is used to objectively quantify the impairment caused by a stroke. | Enrollment, baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in gait speed (km/h) during patients´ comfort speed | Gait speed will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in gait cadence (steps/min) during patients´ comfort speed | Gait cadence will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in paretic and non-paretic leg step length (cm) during patients´ comfort speed | Change in paretic and non-paretic leg step length will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in duration of stance phase as percentage of gait cycle (%) for paretic and non-paretic limb during patients´ comfort speed | Change in duration of stance phase will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in double stance phase as percentage of gait cycle (%) during patients´ comfort speed | Change in double stance phase will be assessed by treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in ground reaction force (N) for paretic and non-paretic limb during patients' comfort speed | Change in ground reaction force will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in plantar pressure distribution (N/cm2) for paretic and non-paretic limb during patients´ comfort speed | Change in plantar pressure distribution will be assessed by instrumented treadmill gait analysis system (Zebris Medical GmbH, FDM-T system). | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in Functional Ambulatory Category FAC | Functional walking test that assess gait ability with 6 levels ranging from 0 to 5 on the basis of the amount of physical support required. | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in Fugl-Meyer Assessment | Fugl-Meyer Assessment uses to examine the sensory-motor function and coordination of affected lower extremity. | baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in functional magnetic resonance imaging activation magnitude | Functional MRI activation magnitude, calculated as difference in BOLD signal between task and rest, will be assessed within pre-defined gait-related brain regions of interest (ROIs), i.e., sensorimotor cortex, premotor cortex, supplementary motor area, brainstem and cerebellum. Change in these ROI parameters over time will be statistically tested within group and the regional post-training minus pre-training difference in each group will be submitted to between-group analysis. | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 
| Change in functional magnetic resonance imaging activation volume | Functional MRI activation volume, summed over significantly activated voxels, will be assessed within pre-defined gait-related brain regions of interest (ROIs), i.e., sensorimotor cortex, premotor cortex, supplementary motor area, brainstem and cerebellum. Change in these ROI parameters over time will be statistically tested within group and the regional post-training minus pre-training difference in each group will be submitted to between-group analysis. | Baseline (before beginning of inpatient RHB), after two weeks (at the end of inpatient RHB), and in follow-up (after three and six months after stroke onset) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gait, Ischemic Stroke, Stroke rehabilitation, Physical Therapy, Exoskeleton Device, Walking speed, Gait Analysis, Functional Magnetic Resonance Imaging