A randomized controlled study incorporating an electromechanical gait machine, the Hybrid Assistive Limb, in gait training of patients with severe limitations in walking in the subacute phase after stroke

Early onset, intensive and repetitive, gait training may improve outcome after stroke but for patients with severe limitations in walking, rehabilitation is a challenge. The Hybrid Assistive Limb (HAL) is a gait machine that captures voluntary actions and support gait motions. Previous studies of HAL indicate beneficial effects on walking, but these results need to be confirmed in blinded, randomized controlled studies. This study aimed to explore effects of incorporating gait training with HAL as part of an inpatient rehabilitation program after stroke. Thirty-two subacute stroke patients with severe limitations in walking were randomized to incorporated HAL training (4 days/week for 4 weeks) or conventional gait training only. Blinded assessments were carried out at baseline, after the intervention, and at 6 months post stroke. The primary outcome was walking independence according to the Functional Ambulation Categories. Secondary outcomes were the Fugl-Meyer Assessment, 2-Minute Walk Test, Berg Balance Scale, and the Barthel Index. No significant between-group differences were found regarding any primary or secondary outcomes. At 6 months, two thirds of all patients were independent in walking. Prediction of independent walking at 6 months was not influenced by treatment group, but by age (OR 0.848, CI 0.719–0.998, p = 0.048). This study found no difference between groups for any outcomes despite the extra resources required for the HAL training, but highlights the substantial improvements in walking seen when evidence-based rehabilitation is provided to patients, with severe limitations in walking in the subacute stage after stroke. In future studies potential subgroups of patients who will benefit the most from electromechanically-assisted gait training should be explored.


Background
Stroke is a common disorder worldwide and hemiparesis is the most common acute impairment and often impacts on gait function (Duncan 2005, Jorgensen 1995. While motor control is improved in most patients during the months following the ictus, a substantial proportion are left with impaired mobility. Even though several studies indicate that early, intensive training of motor functions may accelerate postacute recovery and improve the final outcome there is a recognised need for more effective treatment in this respect (Langhorne 2009).
Several studies have explored the value of various technologies that are designed to enable more intensive gait training programs (Mehrholtz 2012). While there is evidence that body weight supported gait training on a treadmill may be beneficial early after stroke (Moseley 2005), there is a need for more studies to demonstrate the additional value of training supported by electromechanical devices, which may not only enable more intensive training but also more efficient utilisation of therapist time.
Devices used to support gait training after stroke include treadmill training with or without body weight support (BWS). These devices may be combined with electromechanical "gait machines", which can allow more reproducible gait movements when compared to when a therapist move the patients legs. Gait machines are often categorized as machines using an end-effector principle and machines that function as exoskeletons (Hesse 2010). Machines based on the end-effector principle use foot plates that move the feet in a controlled gait pattern and allow the operator to adjust many aspects of locomotion, such as speed, stride length and step height. In contrast, exoskeletons are attached to the patient and function as an external skeleton. Exoskeletons for lower extremities have joints matching the patient's lower limb joints and motors that drive movements over these joints to assist leg movements. Recent reviews conclude that more data is needed with regard to the optimal type of electromechanical device for stroke patients (Merholtz 2012) and that there is a need for further development of concepts and devices as well as their evaluation in clinical trials (Dobkin 2009, Pennycott 2012).
The Hybrid Assistive Limb has been developed at the University of Tsukuba and Cyberdyne Inc in Tsukuba, Japan, in a group headed by professor Sankai (Kawamoto 2009, Kawamoto 2010. The exoskeleton provides support according to the patient's condition by a control algorithm and supporting devices, where each joint (left and right hip and left and right knee) can be controlled separately. HAL offers a hybrid control algorithm consisting of "Cybernic Voluntary Control", based on the users voluntary muscle activation and bioelectrical signals, such as by electromyographical input, and a "Cybernic Autonoumous Control", based on the users constitution, condition and intensions and using a variety of other signals such as mechanical input. HAL offers a new principle and allows training early after stroke as soon as postural control is sufficient to allow an upright position. Training by use of HAL may be performed with or without BWS. Our group has recently finalised a study that demonstrates the feasibility and safety of HAL for gait training in patients with impairment early after stroke (Nilsson 2013). This has also been demonstrated after other chronic conditions (Kubota 2013).

Aim and hypotheses of the study
To compare gait function after training with HAL with gait function after conventional gait training as part of an in patient rehabilitation program early after stroke. The primary outcome will be gait performance after the training period and the secondary outcome will be gait performance 6 months after stroke according to the Functional Ambulation Categories. Another outcome will be length of stay in hospital. We hypothesize that training with HAL will improve their gait function significantly more when compared with conventional gait training.

Study design
A randomized controlled study.

Patients
Eligible will be patients living in the Stockholm region and who are admitted to the University Department of Rehabilitation Medicine for inpatient rehabilitation early after stroke from January 2014 until December 2014.
Inclusion criteria: less than eight weeks since stroke; unable to walk independently due to lower extremity paresis (i.e. Functional Ambulation Categories (FAC score 0-1) with or without somatosensory impairment and with or without spasticity; able to sit on a bench with/without supervision at least five minutes; sufficient postural control to allow upright position in standing with aids and/or manual support; ability to understand training instructions as well as written and oral study information and to express informed consent; body size compatible with the HAL suit.
Exclusion criteria: contracture restricting gait movements at any lower limb joint (hip, knee, ankle); cardiovascular or other somatic condition incompatible with intensive gait training; severe, contagious infections (e. g. with Methicillin Resistant Staphylococcus Aureus (MRSA) or Extended Spectrum Beta-Lactamase (ESBL) bacteria).

Training program and randomisation
Training with HAL will be performed in one session per day, four days per week during four weeks. HAL will be used according to the manufacturer's manual. Time for each session will be individualised but not exceed 60 minutes/session (effective time). Training with HAL will be performed in combination with body-weight support and treadmill. The training program will be performed by two physiotherapists, who have been trained in the HAL method in Tokyo.
Conventional gait training will be according to current practice, may include use of treadmill and body weight support, and will be documented in the clinical research file (CRF).
Randomisation will be performed by a nurse, who is not otherwise involved in the study according to a block design.