Effectiveness of a Powered Exoskeleton Combined With FES for Patients With Chronic SCI: a RCT

Study Overview
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Brief Summary
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While there are a number of prospective studies evaluating powered exoskeletons in SCI patients, to date, not a single well-designed, randomized clinical trial has been published. However, there is evidence for beneficial effects of over-ground exoskeleton therapy on walking function post-intervention from a meta-analysis on non-randomized, uncontrolled studies. Functional electrical stimulation (FES), on the other hand, is a common and established method for the rehabilitation of persons with SCI and has been demonstrated to be beneficial in, e.g., improving muscle force, power output and endurance. Combining FES and overground robotic therapy within the same therapy session could potentially merge and potentiate the effects of each separate treatment, making it a very powerful and efficient therapy method. Up to date, however, comparative studies evaluating benefits of this combined approach (i.e., powered exoskeleton and FES) to robotic therapy without FES are missing.

Detailed Description
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Paraplegia is a serious event that leads to a complete or partial loss of motor, sensory and vegetative functions. Regaining of gait, balance and mobility are important priorities for persons with a spinal cord injury (SCI). In the last decade the technological development of exoskeletons allowed persons with SCI getting closer to their desired goal. Wearable robotic exoskeletons are motorized orthoses that facilitate untethered standing and walking over ground. Supporting multiple step repetitions while having full weight bearing on the body, these devices represent a task-specific and -oriented training approach for rehabilitation of gait function after SCI. However, in cases where rehabilitation of gait function is not the aim, the need to target secondary health problems associated with SCI like pain, spasticity, bowel and bladder function can still be a rationale for engaging in exoskeleton training. Another well-established technique for the treatment of such secondary health problems is functional electrical stimulation (FES). FES is a common and established method for the rehabilitation of persons with spinal cord injury. Several studies have documented positive effects of FES like, e.g., avoiding disuse and denervation atrophy, improving muscle force, power output and endurance, changing muscle fibre type, increasing cross sectional area of muscles, increasing muscle mass, activation of nerve sprouting, motor learning and reducing spasticity. In addition, FES has been shown to improve bladder, bowel and sexual function, cardiovascular fitness (by increasing aerobic capacity), reduce body fat mass and prevent and treat pressure ulcers by increasing muscular blood flow. Moreover, FES treatment has also been shown to have an impact on body function by improving lower limb function as well as trunk stability and function. The power elicited by the muscle through electrical stimulation can be used for locomotion. To do so, undesired limb motion is often restricted by passive orthoses or pedals in order to efficiently use the muscle contraction from the user to safely provide the power for forward propulsion. The usefulness of such systems, however, is often limited due to the rapid initiation of muscle fatigue. This is one reason (amongst others) why hybrid FES-robotic solutions have been developed, which supplement the power produced by electrical stimulation with motorized assistance. This approach reduces the power that needs to be produced by the muscles, allowing for FES application for longer training sessions before fatigue occurs. By doing so, such hybrid powered exoskeletons offer the physiological health benefits similar to FES cycling, while simultaneously enhancing the user's mobility. The addition of FES to a powered exoskeleton also synergistically reduces the motor torques of the device, reducing battery drain and therefore increasing the maximum range of the exoskeleton. While it sounds perfectly reasonable, from a technical and physiological perspective, to combine powered exoskeletons and FES to such hybrid bionic systems, there is only anecdotal evidence for their clinical usefulness and efficacy in patients with SCI. Here the investigators propose a randomized controlled trial investigating the effect of the combined application of the EksoNR powered exoskeleton (Ekso Bionics, Richmond, CA, USA) and FES (FES RehaMove2, Hasomed, Magdeburg, Germany) compared to Ekso therapy alone on functional outcomes and secondary health parameters.

Official Title
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Effectiveness of a Powered Exoskeleton Combined With Functional Electric Stimulation for Patients With Chronic Spinal Cord Injury: a Randomized Controlled Trial

Conditions
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Spinal Cord Injuries, Gait Disorders, Neurologic

Intervention / Treatment
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* Device: Ekso (EksoNR, Ekso Bionics)
* Device: FES (RehaMove2, Hasomed)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: chronic, incomplete SCI (> 1 year, AIS B-D) traumatic or non-traumatic lesion capacity to stand up and perform a 10MWT with or without medical aids partially wheelchair dependent intact lower motoneuron on the segmental innervation level of M. glutaeus maximus, Mm. ischiocrurales, M. tibialis anterior and M. quadriceps (to guarantee the stimulability with FES) Exclusion Criteria: Exoskeleton device related contraindications: > 100 kg body weight; Body height: < 155 cm or > 190 cm; pelvic width: > 46 cm orthopedic limitations (acute fractures of the lower limb) contractures heterotrophic ossification spasticity (modified Ashworth Scale >3) skin injuries of the lower limbs in areas where the skin has contact with the exoskeleton Unstable circulation (unable to stand for at least 10 minutes) acute deep vein thrombosis pregnancy (tested in women of childbearing age (15 - 49 years))

Ages Eligible for Study
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Minimum Age: 18 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: assessor-blinded, exploratory, randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ekso and FES<br>Participants will train for 8 weeks, 3 times per week (i.e. 24 sessions in total) for 30 minutes effective training time per session using the EksoNR powered exoskeleton combined with gait-synchronized FES using the FES RehaMove2. | Device: Ekso (EksoNR, Ekso Bionics)<br>* The EksoNR is a powered exoskeleton designed to be used in a rehabilitation setting. The device meets the provision of the Council Directive 93/42/EEC concerning medical devices and is used for gait training in neurorehabilitation.<br>Device: FES (RehaMove2, Hasomed)<br>* RehaMove 2 sends electrical impulses via electrodes to nerves to evoke muscle contraction. The device meets the provision of the Council Directive 93/42/EEC concerning medical devices.<br>|
| Active Comparator: Ekso without FES<br>Participants will train for 8 weeks, 3 times per week (i.e. 24 sessions in total) for 30 minutes effective training time per session using the EksoNR powered exoskeleton without applying FES. | Device: Ekso (EksoNR, Ekso Bionics)<br>* The EksoNR is a powered exoskeleton designed to be used in a rehabilitation setting. The device meets the provision of the Council Directive 93/42/EEC concerning medical devices and is used for gait training in neurorehabilitation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in preferred walking speed from baseline (Visit 1) to post-training (Visit 2) as measured by using the 10MWT | The 10MWT is a quantitative measurement of lower extremity function. Patients are instructed to walk 10 meters at their preferred speed. Time is measured while the individual walks the set distance (10 meters). The distance covered is divided by the time it took the individual to walk that distance. | within 3 days post-training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline (Visit 1) in preferred walking speed, measured by the 10MWT, at Visit 3 | The 10MWT is a quantitative measurement of lower extremity function. Patients are instructed to walk 10 meters at their preferred speed. Time is measured while the individual walks the set distance (10 meters). The distance covered is divided by the time it took the individual to walk that distance. | 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in maximal walking speed measured by the 10MWT | The 10MWT is a quantitative measurement of lower extremity function. Patients are instructed to walk 10 meters at their preferred speed. Time is measured while the individual walks the set distance (10 meters). The distance covered is divided by the time it took the individual to walk that distance. | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in gait function as measured by the Walking Index for Spinal Cord Injury II (WISCI II) | WISCI is an ordinal scale that is used in clinical trials as a tool to asses walking function. It captures the extent and nature of assistance a person with SCI requires to walk. This assessment index includes a rank ordering along a dimension of impairment, from the level of most severe impairment (level 0) to least severe impairment (level 20). The level is based on the use of devices, braces and physical assistance of one or more persons. The ranking of severity is based on the severity of impairment and not on functional independence in the environment. | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in endurance as measured by the 6 Minute Walk Test (6mWT) | The 6mWT is a sub-maximal test that is used as a global and easy indicator of the loco-motor performance. Individuals are instructed to walk as far as possible during 6 minutes, taking rests whenever required. The distance covered and the number/time of rests required are recorded. | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in balance function as measured by the Mini-Balance Evaluation Systems Test (Mini-BESTest) | The Mini-BESTest is a 14-item test which targets dynamic balance by assessing 4 subsystems influencing balance control: anticipatory postural adjustments, postural responses, sensory orientation and balance during gait. Items are scored on an ordinal scale ranging from 0 to 2 (0=unable, 2=normal), with a total score of 28 points. | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in the standing balance assessment using the zebris pressure distribution measurement platform (zebris Medical GmbH, Isny, Germany) | Patients stand upright with feet positioned in the outline of the force-plate, keeping their eyes open/closed and looking forward during the entire test. The system records the path of the centre of pressure (COP) and calculates the traveled distance, the average speed and the area of the 95% confidence ellipse of the COP during the measurement. | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in strength using the Medical Research Council Manual Muscle Test (MRC MMT) | The MRC MMT is a standardized set of assessments to measure muscle strength. The muscle scale grades muscle power on a scale of 0 to 5 in relation to the maximum expected for that muscle (0=no contraction, 5=normal power). | within 3 days post-training, 3 months post intervention | 
| Changes from baseline at Visit 2 and Visit 3 in Quality of Life will be assessed according to the International SCI Quality of Life Basic Data Set | Quality of Life will be assessed according to the International SCI Quality of Life Basic Data Set. | within 3 days post-training, 3 months post intervention | 
| Training duration in the Exoskeleton | The training duration in the Exoskeleton in minutes will be automatically analysed and documented by the Ekso operating software (Ekso Pulse). | week 1 to week 8 | 
| Training intensity in the Exoskeleton | Intensity of the training will be automatically analysed and documented as steps per minutes by the Ekso operating software (Ekso Pulse). | week 1 to week 8 | 
| Training volume in the Exoskeleton | Training volume will be automatically analysed and documented as number of steps executed for the training duration. | week 1 to week 8 | 
| Cardio-respiratory measurement | Participants will undergo an analysis of the cardio-respiratory demand of the respective therapy method using the K5 wearable metabolic system (COSMED). | week 2, week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCI, Functional Electrical Stimulation, Exoskeleton, Robotic device, Robotic overground gait training