Exoskeleton-assisted Training to Accelerate Walking Recovery Early After Stroke: the TARGET Phase II Study

Study Overview
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Brief Summary
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Phase II: Investigating the effects of additional robot-assisted gait training either initiated early (2 weeks post-stroke) or delayed (8 weeks post-stroke) after stroke onset.

Detailed Description
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GENERAL: Pre-clinical research has pointed towards a time window of enhanced responsiveness to therapy early after stroke. For example, training has led to substantial recovery if initiated 5 or 14, but not 30 days post-stroke in a rodent model (Biernaski 2004). It is suggested that this early period is characterized by heightened levels of plasticity and that training can exploit this leading to improved outcome. The typically observed non-linear recovery pattern in stroke survivors (Kwakkel 2004) might suggest that similar mechanisms are induced in the human brain, however clinical research on this is disappointingly sparse. In two closely inter-related phases, we aim to examine the biomechanical changes related to walking recovery in general (Phase I) and the specific effects of robot-assisted training (Phase II). By that, we aim to detect a time window in stroke survivors which resembles the same characteristics as observed in animal models. To initiate gait training at an early stage, when patients usually present severe weakness and balance deficits, a mobile exoskeleton is used which is developed to provide intensive walking practice. OBJECTIVES: (II.a) Are stroke survivors who train with the assistance of a robot at an early stage more likely to achieve independent walking? (II.b) Does additional robot-assisted training modulate the recovery of standing and walking ability by enhancing behavioral restitution?

Official Title
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A Temporal Analysis of the Robustness of Hemiplegic Gait and Standing Balance Early After sTroke - the TARGET Research Project

Conditions
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Stroke, Paresis, Gait, Hemiplegic

Intervention / Treatment
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* Behavioral: Exoskeleton-assisted gait training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First-ever, MRI- or CT-confirmed, ischemic or hemorrhagic, anterior circulation stroke Age: 18 - 90 years Baseline assessments within the first 14 days after stroke onset Unable to walk independently at baseline (FAC <3) Moderate to severe weakness of the lower limb at baseline (MI </=75) Pre-morbid independence in activities of daily living (mRS </=2) and gait (FAC >3) Able to communicate and comprehend Sufficient motivation to participate Provided a written informed consent Exclusion Criteria: No other neurological condition affecting motor functions of the lower limbs Pre-existing musculoskeletal impairment severely affecting the gait pattern Body weight > 100 kg Severe spasticity or contractures that prevent safe use of the exoskeleton Medically unstable to participate in additional therapy sessions

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: Participants will be randomly assigned to either the early group or delayed group. Both groups will be provided a dose- and content-controlled intervention in addition to usual care. The early group will receive this intervention at approximately 2 weeks post-stroke and the delayed group at 8 weeks post-stroke. As such, this study is explicitly designed to investigate the effects of time to initiate rehabilitation on recovery outcomes.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Experimental Group<br>N = 20 Intervention = 1-hour sessions of exoskeleton-assisted gait training, using the Ekso GT (Ekso Bionics, CA, USA) in addition to standard care Frequency = 4 times per week for 4 weeks, provided within the first 6 weeks post-stroke | Behavioral: Exoskeleton-assisted gait training<br>* In the experimental groups, participants are provided with 1-hour sessions of gait training with robot assistance, 4 times per week for 4 weeks. Assistance is provided by the Ekso GT (Ekso Bionics, Richmond, CA, USA), an exoskeleton consisting of fitted metal braces that supports the legs, feet, and trunk of the patient. Powered motors drive knee and hip joints in the sagittal plane to assist during standing up and walking over level surfaces. Steps are initiated if an active weight-shift towards the stance leg is performed by the patient. The provided assistance in stance and swing is adaptable to the patient's ability and can be adjusted for each leg separately.<br>|
| Experimental: Delayed Experimental Group<br>N = 20 Intervention = 1-hour sessions of exoskeleton-assisted gait training, using the Ekso GT (Ekso Bionics, CA, USA) in addition to standard care Frequency = 4 times per week for 4 weeks, provided between week 8 and week 12 post-stroke | Behavioral: Exoskeleton-assisted gait training<br>* In the experimental groups, participants are provided with 1-hour sessions of gait training with robot assistance, 4 times per week for 4 weeks. Assistance is provided by the Ekso GT (Ekso Bionics, Richmond, CA, USA), an exoskeleton consisting of fitted metal braces that supports the legs, feet, and trunk of the patient. Powered motors drive knee and hip joints in the sagittal plane to assist during standing up and walking over level surfaces. Steps are initiated if an active weight-shift towards the stance leg is performed by the patient. The provided assistance in stance and swing is adaptable to the patient's ability and can be adjusted for each leg separately.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change on the Fugl Meyer motor assessment - subscale lower extremity (FM-LE) | This scale measures the level of of volitional, selective control of muscles of the paretic lower limb. Scoring: This scale is scored from 0 (no reflex activity) to 34 (volitional movement out of synergies). | Longitudinal change is determined between the following time points: Baseline (0-1 week post-stroke), 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trunk Control Test - item sitting balance | Sitting balance is part of the prognostic model used to stratify patients at baseline. Scoring: 0 - 1 (able to sit independently without support of the legs or trunk 30 seconds) | Baseline (0-1 week post-stroke) | 
| Motricity Index - subscale lower extremity (MI-LE) | Strength of major muscle groups of the paretic lower limb is assessed. At baseline this is part of the prognostic model used to stratify patients. Scoring: This scale is scored from 0 (no muscle activity) to 99 (normal strength over full range of motion in hip flexors, knee extensors and ankle dorsiflexors). | Baseline (0-1 week post-stroke), 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 
| Berg Balance Scale - item standing unsupported | This item of the BBS indicates the ability to stand independently and therefore reflects the process of functional walking recovery within the first 6 months post-stroke. Scoring: This scale includes 5 levels (0-4), ranging from unable to stand 30 seconds unassisted (0) to able to stand safely 2 minutes (5). | Baseline (0-1 week post-stroke), 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 
| Functional Ambulation Categories (FAC) | This scale indicates the ability to walk independently and therefore reflects the process of functional walking recovery within the first 6 months post-stroke. Scoring: This scale includes 6 levels (0-5), ranging from nonfunctional ambulation (0) to ambulate independently, on level and non-level surfaces including stairs and inclines (5). | Baseline (0-1 week post-stroke), 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 
| Kinetic analyses of standing balance & gait | Dual-force plate measurements are able to indicate the adopted control strategies for standing balance and walking. These analyses are used to distinguish between behavioral restitution and the use of compensation strategies. | 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 
| EMG analyses of standing balance & gait | EMG analyses will be performed to gain insights in the muscle recruitment of patients during standing and walking. These analyses are used to distinguish between behavioral restitution and the use of compensation strategies. | 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke | 
| Spatio-temporal analyses of gait | Assessing comfortable (self-selected) speed and spatial/temporal symmetry of gait over a short distance. | 3 weeks post-stroke, 5 weeks post-stroke, 8 weeks post-stroke, 12 weeks post-stroke, 24 weeks post-stroke. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, rehabilitation, robotics