Home rehabilitation supported by a wearable soft-robotic device for improving hand function in older adults: A pilot randomized controlled trial

Background New developments, based on the concept of wearable soft-robotic devices, make it possible to support impaired hand function during the performance of daily activities and intensive task-specific training. The wearable soft-robotic ironHand glove is such a system that supports grip strength during the performance of daily activities and hand training exercises at home. Design This pilot randomized controlled clinical study explored the effect of prolonged use of the assistive ironHand glove during daily activities at home, in comparison to its use as a trainings tool at home, on functional performance of the hand. Methods In total, 91 older adults with self-perceived decline of hand function participated in this study. They were randomly assigned to a 4-weeks intervention of either assistive or therapeutic ironHand use, or control group (received no additional exercise or treatment). All participants performed a maximal pinch grip test, Box and Blocks test (BBT), Jebsen-Taylor Hand Function Test (JTHFT) at baseline and after 4-weeks of intervention. Only participants of the assistive and therapeutic group completed the System Usability Scale (SUS) after the intervention period. Results Participants of the assistive and therapeutic group reported high scores on the SUS (mean = 73, SEM = 2). The therapeutic group showed improvements in unsupported handgrip strength (mean Δ = 3) and pinch strength (mean Δ = 0.5) after 4 weeks of ironHand use (p≤0.039). Scores on the BBT and JTHFT improved not only after 4 weeks of ironHand use (assistive and therapeutic), but also in the control group. Only handgrip strength improved more in the therapeutic group compared to the assistive and control group. No significant correlations were found between changes in performance and assistive or therapeutic ironHand use (p≥0.062). Conclusion This study showed that support of the wearable soft-robotic ironHand system either as assistive device or as training tool may be a promising way to counter functional hand function decline associated with ageing.

diseases frequently experience difficulties in performing activities of daily living (ADL) due to a decline in hand function. They often need personal and/or assistive devices to carry out ADL.
However, personal assistance will not result in more independence in performing ADL while assistive devices have the potential to provide the assistance that is necessary to perform ADL independently. New technological innovations can support the functional performance of the arms and hands directly by a wearable soft robotic device assisting a person's own function.
By integrating both an assistive robotic device with exercise training, performance of ADL can be enhanced directly and/or via an improved arm and hand function after prolonged use of the hands.

Objective:
The primary objective of the present study is to examine the orthotic and therapeutic effect of the ironHand (iH) system, consisting of both an assistive and therapeutic module, by elderly and diagnosed patients with hand function problems, after using the iH system for a four weeks training period at home. Secondary objectives are related to user acceptance, including usability, satisfaction, motivation and compliance.

Study design:
A randomized controlled trial design will be conducted, in which both the elderly and patient population will be randomized into three groups; the iH assistive group, the iH therapeutic group and the control group. Evaluation is based on one baseline measurement and one evaluation measurement within one week after the intervention period of four weeks.

Study population:
In total, twenty-seven elderly and fifteen stroke patients with an age over 55 years, will participate in this study.

Intervention (if applicable):
The intervention period for all three groups will last for a period of four weeks. The iH assistive group will use the wearable robotic device during ADL at home and the therapeutic iH group will use the wearable robotic device as a training tool using games via the patient user interface. Participants of the control group do not follow an intervention program. In the iH assistive group, participants are recommended to use the wearable robotic device for 180 minutes a week during ADL at home. The participants in the iH therapeutic group are recommended to train the hand 3 times a week for 60 minutes by performing game exercises while wearing the robotic device to support hand opening and strength and to control the game exercises on a screen. During the four weeks intervention period, all three groups will be monitored by a therapist.

Main study parameters/endpoints: Jebsen-Taylor Hand Function Test
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The iH system may have a beneficial effect on hand function, by directly improving functional task performance or by using it as a training tool. It may be possible that the functional use of the hand improves, allowing people to be more active in ADL and to maintain or improve their health status. However, the exact benefit cannot be predicted, because this is the topic of the current research.
The risks for the subjects are limited to a minimum. The iH system is a device that facilitates hand grip and opening as initiated by the user him/herself. It provides support only when necessary based on voluntary, active initiation by the person him/herself. Furthermore, the iH system is a so-called soft-robotics device, constructed from soft materials that are comfortable to wear and compliant with human movement. This prevents potential occurrence of pressure points for example. All movements conducted during the study will consist of arm/hand movements that normally occur in ADL and within the abilities of each individual. Additionally, all the evaluation measurements used in these studies are non-invasive and involve no risks for the subjects.

INTRODUCTION AND RATIONALE
The hand is important to perform activities of daily living (ADL). However, many people experience a loss of hand function as result of acute diseases (e.g., stroke), chronic diseases (e.g., arthritis) or ageing. The experience of a decline in hand function can be a result of a reduction in grip strength, finger dexterity, sensation or muscle coordination [1][2][3]. As a consequence, people with a loss of hand function have difficulties with holding and manipulating objects [4], subsequently leading to difficulties with independently performing ADL [5][6][7]. These limitations can have a negative effect on their participation in society or quality of life [8][9][10][11]. Therefore, it is important to restore and maintain hand motor function of people with an impaired hand function.
Different approaches can be used to improve independence in ADL, such as personal assistance, assistive devices or hand exercise training. In contrast to personal assistance, assistive devices and hand exercise training may result in increased independence in performing ADL without relying on others.
Assistive devices have the potential to provide the assistance that is necessary to perform independently ADL [12]. There are many assistive devices available that people can use to compensate for the loss of functionality in their upper limb motor function [13,14]. These assistive devices can range from simple assistive tools (e.g. knife with an adapted handle) to fully robotic systems that can substitute activities performed by people themselves in the case of very severe limitations (e.g. JACO) [15,16]. However, many of these simple assistive tools are only usable for a specific task, while the fully robotic systems allow more functionality, but are not portable (except when mounted on a wheelchair), very expensive and too bulky to use unobtrusively in daily life. Furthermore, these fully robotic systems often completely substitute the function of the person [17][18][19]. Therefore, new technological innovations are needed that can support the arms and hands directly in a wide range of functional tasks. A promising approach is a wearable soft robotic device assisting a person's own function.
Another approach to improve hand motor function is hand exercise training consisting of high repetition and intensive task-specific exercises [20,21]. However, intensive conventional hand training exercise takes a lot of effort from patients and therapists and is expensive [22,23].
Therefore, development of robotic devices that can assist in providing training of upper limb motor function in people with functional limitations and disabilities is increasing rapidly [13,24].
First, these robotic devices can increase independent training with more intensive and repetitive exercises [20]. Second, robotic devices can give adequate objective and reliable feedback about patients' progress and performance during therapy [25]. Finally, research shows that robot-assisted therapy can reduce motor impairments of the upper limb in stroke patients [24][25][26].
When as assistive robotic device is wearable and usable in daily life, the opportunity exists to combine direct assistance from a robotic device with exercise training. With a wearable assistive device, performance of functional activities can be enhanced directly, while using the arms and hands repeatedly during functional daily activities, which provides intensive and taskspecific training at the same time. Ultimately, it is possible that unsupported arm and hand function improves after prolonged use. To allow prolonged use of such an robotic device in everyday activities at home, an easy to use and affordable system (ironHand (iH) system) is developed within the current project, to support elderly people and patients with hand motor problems during ADL and rehabilitation, based on the concept of a wearable soft-robotic glove.
The iH system provides support for grip and hand opening in a natural and intuitive way, but only if the user initiates the movement actively. Furthermore, it will give only the amount of support that is needed. This will make sure that people maintain an active contribution to movements at all time. By adding a personalized computer gaming environment, specific training exercises can be provided as well. Therefore, this study explores whether prolonged use of such an assisting glove during ADL at home can enhance functional performance, and compare this with applying such a robotic device as a training tool at home. By comparing the assistive function with the training function, it is assessed whether assistance or training contributes most to the potential effects.
In the first stage of user testing with the iH system during 2015 (P15-11), both user acceptance and impact on functional performance were investigated [27]. Participants perceived the concept of the iH system to be useful, pleasant and meaningful. Although no major usability issues were observed, functional task performance was slower with assistance from the iH system than without iH system. A continuation of the learning curve during functional task performance after 3 repetitions across 2 sessions indicates that increased performance can be expected in case of a longer time to get acquainted to the iH system. Therefore, design adaptations of the iH system were done to further improve system performance and usability.
There were no adverse events observed or reported during or after the study. In the current second stage of user testing, the adapted iH system will be tested in-depth and in a larger group of users. In contrast to the focus on user acceptance in the previous testing phase, the focus of the current study is on the therapeutic effects of the iH system (relating to the assisting and training function, respectively) on functional performance, in addition to user acceptance, actual use and potential impact on quality of life (QoL).

OBJECTIVES
Primary Objective: To examine whether prolonged use of the iH system for assisting and/or training at home improves functional performance of the most-affected arm and hand Secondary Objective(s): To explore the user acceptance of using the iH system at home, either as assistive or as training tool, including usability, satisfaction, motivation and compliance To examine changes in hand strength due to prolonged use of the iH system (either as assistive or as training tool) To examine whether elderly or patients improve their overall QoL after prolonged use of the iH system (either as assistance or as training tool) To examine changes in amount of use of the most-affected hand after using the iH system as assistance or as training tool To explore potential relations between user acceptance, amount of use, changes in hand function and QoL

STUDY DESIGN
The present study examines the therapeutic effect of the iH system, either used as assistance or as training tool at home, to improve unsupported arm and hand function of both elderly and patients with hand function problems in ADL. Since this study is part of a European project, similar tests will be done in Sweden and Switzerland besides the Netherlands. The part described in this protocol represents the Dutch part of the study, which involves the participation of the National Foundation for the Elderly (NFE, Bunnik) and Roessingh Research and Development (RRD, Enschede).
This study consists of a randomized controlled trial with two evaluation measurements. The baseline measurement will be performed a week before the start of the study (T0). Afterwards, participants of both the elderly and patient population (via two separate randomization procedures) will be randomized into three equal groups. Group 1 will use the iH assistive system (AS) during ADL at home (iH assistive group), group 2 will use the iH therapeutic system (TS) as a training tool at home (iH therapeutic group) and group 3 will not perform any intervention at home (control group) during the intervention period of four weeks. Within one week after the intervention period a post-evaluation will be performed (T1). During both evaluation sessions, the participants will perform various hand function tests with and without the glove to assess the therapeutic effect of the iH system (modes), as well as the direct influence of the glove assistance. NFE and RRD have different sizes of both left and right hand gloves available to ensure that the participant has the most suitable glove for him/her. An overview of the study is given in Figure 1.

Population (base)
In the present study, NFE and RRD together will recruit 27 elderly participants with perceived hand function problems and 15 patients diagnosed with stroke. The elderly will be selected from the current databases or network of NFE and RRD to participate in this study. The stroke patients will be recruited at Roessingh Center for Rehabilitation, Enschede. A rehabilitation physician will identify stroke patients suitable for the study, based on the selection criteria.
After the selection of suitable subjects, the researcher will contact the potential participants by phone and will provide him/her, both verbally and in writing, with the necessary information about the study, if the person is interested. The information letter explains the goal of the study and their expected involvement. All subjects will be informed that they can stop their involvement at any moment, without giving any reason and without experiencing any disadvantage. All subjects will have to provide written informed consent, prior to their involvement in the study.

Inclusion criteria
In order to be eligible to participate in this study, the elderly population must meet all of the following criteria: Elderly adults over the age of 55 years Experience difficulties in performing ADL due to a decline in hand function Absence of wounds on their hands that can give a problem when using the glove

Exclusion criteria
A potential subject of either study population who meets any of the following criteria will be excluded from participation in the study in the case of: Severe sensory problems of the most-affected hand Severe acute pain of the most-affected hand Participation in other studies that can affect functional performance of the arm and hand Insufficient knowledge of the Dutch language to understand the purpose or methods of the study

Sample size calculation
The nature of the current study is explorative, to gain understanding about the potential of a wearable robotic glove to support functional abilities and/or improve arm/hand function, in addition to examining users' perspectives of using such technology to support their ability to perform ADL. Therefore, a power calculation is not applicable. The numbers are based on what is believed to be sufficient to gather the intended information and will be feasible and practical to achieve during the course of the study. The study will be replicated with the same

TREATMENT OF SUBJECTS
The researchers involved in the study receive an extensive training about how to handle and operate the iH system by personnel from the technical project partners prior to the start of the study. Also, they are instructed on how to explain use of the iH system to participants, following a standard procedure.
Two evaluation sessions will be performed. The baseline assessment will take place one week before the intervention period and the post-evaluation assessment will take place within one week after the intervention period. During both evaluations first a calibration measurement will be performed, to assess the proper amount of support to be set in strength and hand opening.
Thereafter, an extensive set of hand function tests will be performed. These hand function tests will be performed with and without the glove to assess the direct impact of the iH system.
At the end of the hand function tests, participants will be asked about their experiences and perceived ability of using the iH system (either as assistance or training tool).

Investigational product/treatment
After the baseline assessment, the participants will be randomly assigned to one of the three experimental groups.

iH assistive group
The iH assistive group will use the wearable robotic glove during ADL at home for 4 weeks.
The participants are free to choose for which activities, when and for how long they use the iH AS. However, it is recommended to use the iH AS at least 180 minutes a week during the most common ADL such as dressing/undressing, eating/drinking, functional transfers and personal hygiene. The iH AS will automatically register the amount of use of the device and the participants will register the amount of use in a diary. During the baseline assessment at RRD, the participants will perform a calibration measurement to assess the proper amount of support to be set in strength and hand opening. At the end of this initial session, instructions about all aspects of iH AS use will be given, demonstrated to and practiced with the participant, until the researchers are confident that the participant knows how to use the system at home properly.
The instructions will be repeated upon installation of the iH system at their home.
During the intervention period, researchers will contact the participants once every week by phone, e-mail or a visit, to make sure the participant is doing well and answering any questions about their arm/hand function and ADL or responding to potential problems that might arise.
In addition, there will be a phone number available the participants can call in case of problems.
The participants will also be provided with a manual with most important information about the system.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

iH therapeutic group
The iH therapeutic group will use the wearable robotic glove as a training tool at home for 4 weeks to train their hand function. These participants will be recommended to use the iH TS for (a minimum of) 180 minutes a week. At the end of the baseline session, instructions about all aspects of iH TS use will be given, demonstrated to and practiced with the participant, until the researchers are confident that the participant knows how to use the system at home properly. The instructions will be repeated upon installation of the iH system at their home.
During training, the iH TS will support grip strength and hand opening in a similar way as for the assisting system, but now as applied during training exercises only. These exercises are available on a laptop, running training software with specific exercises for the hand to improve hand motor function and abilities. Based on the sensor readings in the glove, games on a computer screen are controlled by active hand movements of the participant. It is possible to play these games with resistance in the therapeutic glove. However, all exercises are adapted to each person's ability by the therapist.
The participants will follow the instructions on the screen to start each training. The training always starts with a calibration procedure disguised as a game, in order to set the proper game level and the proper amount of support by the device. After the calibration game, the subject will play an exercise game from the therapy plan (is created by the therapist in advance) dependent on the ability and needs of the participant. During the training, the participants will receive feedback to keep him/her motivated. The iH TS will automatically record the actual training time.

Therapeutic exercises
The therapeutic exercises will consist of three different therapeutic goals:

Exercise 1: Submarine
Therapy goal: Simultaneous finger coordination (position) The exercise will require the user to control a robotic submarine equipped with 5 robotic arms that move according to the user's finger angle (signals are coming from the glove). The user will be required to adapt different hand postures in order to collect coins or avoid undesirable items (e.g. bombs). Different coin and bomb locations will encourage the users to adapt different postures and to train the simultaneous coordination of finger flexion and extension. The exercise will require the user to control up and down movements of a character on the screen using hand opening and closing movements. The user will be required to modulate their hand aperture in order to collect points. As the level of difficulty progresses, the glove will provide resistance in either closing or opening the hand (according to the therapeutic need set by the therapist).

Exercise 3: Birds on string
Therapy goal: Sequential finger coordination The exercise will require the user to repeat a sequence of thumb opposition movements. The sequence of movements will be presented to the user on the computer screen by a combination of visual and auditory cues. As the level of difficulty progresses, the sequence of movements will become more complex and will require the user to make use of more fingers in order to achieve the goal.
During the intervention period, researchers will contact the participants once every week by phone, e-mail or a visit, to make sure the participant is doing well and answering any questions about their arm/hand function and ADL or responding to potential problems that might arise.
In addition, there will be a phone number available the participants can call in case of problems.
The participants will also be provided with a manual with most important information about the system.

Control group
The participants of the control group do not follow a specific intervention during the intervention period. They will continue with their normal activity pattern of their most-affected hand. To keep the personal attention the same in comparison with the experimental groups, also these participants will be contacted and asked about their arm/hand function and ADL once every week by phone, e-mail or a visit by the researchers. In addition, there will be a phone number available the participants can call in case of problems.

Use of co-intervention (if applicable)
Use of co-intervention is not applicable.

Escape medication (if applicable)
Escape medication is not applicable.

Name and description of investigational product(s)
The wearable robotic glove (iH system) is based on an existing grip-enhancing glove, SEM glove . The iH system is specifically designed towards the needs of elderly people with declining hand function. The iH system falls under Rule 9 of the Medical device directive, and is considered to be a class IIa device.
The iH system is based on the concept of a soft-robotic glove. The main characteristics of the system are: A cable-driven glove that can provide assistive force to open and close the hand during everyday activities or therapeutic exercises; The assistive force is triggered by an "intention detection" logic that reacts to movement initiation by the user; The glove can be connected to an external PC that allows the user to perform specific, computer-game-like exercises tied to functional tasks in order to keep the motivation to remain active.
The iH system is composed of two main parts: an iH AS and an iH TS (see Figure 2). The iH AS consists of a (1) Control unit and a (2) Glove. The iH TS consists of a (3) Therapeutic platform and (4) Therapeutic software.
The iH AS can be used by itself, i.e. without the iH TS. In this configuration, the iH system improves i) the hand grip strength and endurance following the users grip intention, ii) the hand opening functionality by using passive leaf spring, and iii) the agility of the fingers. It can be used when additional grip strength and endurance is desired, for training on everyday activities and to monitor the user's performance.
The iH AS can also be used in combination to the iH TS to provide specific hand movement therapy and assessments. In this configuration, the iH system supports specific exercises in order to increase muscle strength, coordination, fine motor skills and range of motion in different joints with the aim to improve or maintain motor function. The sensors integrated in the glove allow for control of movement-dependent games. 2) Glove -The main purpose of the glove is to apply the forces generated by the motors in the control unit and to provide the control unit with sensory input from touch sensors at the fingertips. The forces are applied by artificial tendons that are sewn into the glove along the length of the fingers. The glove works together with the control unit that is placed on the hip or on the back of the user. The glove has a slim design and the same look and feel as a regular glove; therefore, it can be worn as any other glove.
The glove functionality also consists of a hand opening function realized by the use of passive 3) Therapeutic platform -The therapeutic platform refers to a computing system (e.g. PC, laptop or tablet) to which the iH AS is connected. This allows the user to train with motivating game-like exercises and visualize his progress through automated reports. The following configurations will be used during the research studies described in this protocol:

Configuration I -Orthotic mode
The system is considered to operate in orthotic mode when the iH AS is not connected to the iH TS. This configuration will be used by the iH assistive group at home. During both evaluation sessions, participants will perform several hand function tests with and without the glove in orthotic mode, wearing it on their most-affected hand to support their hand as desired and needed. The direct impact of the iH AS will be explored, but also user acceptance will be explored.

Configuration II -Therapeutic mode
The system is considered to operate in therapeutic mode when the iH AS is connected to the iH TS. In this configuration, the user can benefit from additional therapeutic training in a motivating environment. This configuration will be used by the iH therapeutic group at home and will not be used in both evaluation sessions.

Summary of findings from non-clinical studies
Findings from non-clinical studies are not applicable in the case of this biomedical device, which is developed for specific interaction with the human body. See IMDD for detailed information about technical testing and product (component) functionality tests.

Summary of findings from clinical studies
Elderly, stroke patients and healthcare professionals, participating in focus groups, have specified requirements regarding: 1) activities that need support of assistive technology, 2) but need further clinical evaluation as described above.

Summary of known and potential risks and benefits
The iH system may have a beneficial effect on hand function, by directly improving functional task performance or by using it as a training tool. It might be possible that the functional use of the hand improves, allowing people to be more active in ADL and to maintain or improve their health status. However, the exact benefit cannot be predicted, because this is the topic of the current research.
The risks for the subjects are limited to a minimum. The iH system is a device that facilitates hand grip and opening as initiated by the user him/herself. It provides support only when necessary based on voluntary, active initiation by the person him/herself. Furthermore, the iH system is a so-called soft-robotics device, constructed from soft materials that are comfortable to wear and compliant with human movement. This prevents potential occurrence of pressure points for example. All movements conducted during the study will consist of hand movements that normally occur in ADL and are within the abilities of each individual. Additionally, all the evaluation measurements used in these studies are non-invasive and involve no risks for the subjects.
In the first stage of user testing with the iH system during 2015 (P15-11), no adverse events were observed. Elderly noticed the support of the iH system and considered the support as pleasant and meaningful. However, several design changes (e.g. fabric of the glove to improve sensation) based on the results of the feasibility study are necessary to further enhance the chance for uptake of the iH system in daily life. This should also improve functional task performance with the glove beyond performance without the glove, before actual use of such assistive system will be beneficial for (and adopted by) elderly [27].
For further information, see IMDD and the associated risk management reports.

Description and justification of route of administration and dosage
The glove applies force to the hand following the same biomechanical constraints as the corresponding muscles. This means that there is no risk that the glove causes unnatural movement of the hand and/or fingers (such as hyperextension). The force to be applied as well as sensitivity of the system will be adjustable to suit the user's needs and limitations by trained personnel. The user will not be able to do any modifications to the configuration of the iH system. It is only possible to choose one of the three different modes with different sensitivity and force values to optimize it for each circumstance. The maximum force of the system is mechanically limited by the motors to a level that is comparable to an average female adult, which means that harmful levels of pressure and/or power can never be reached. In addition, it is important to remember that the device follows the user's own intention. This means that if the user grasps an object harder the glove will provide more force (up to the limited maximum level) but as soon as the user initiates to release the grasp the force applied by the glove will decrease. This gives good feedback to the user and lowers the risk for harm caused by the user dropping things (coffee cup, hot pot, knife etc.).
The same technology has been successfully used in the CE marked SEM™ Glove for a number of years without leading to incidents and/or causing harm. Furthermore, the feasibility study of Nilsson et al. 2013 [29] showed the potential benefit for participants with impaired hand function when they will use such a device as the SEM-glove. Participants with impaired hand function improved their grip while using the SEM-glove.

Dosages, dosage modifications and method of administration
Not applicable.

Preparation and labelling of Investigational Medicinal Product
Not applicable.

Drug accountability
Not applicable.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

Secondary study parameters/endpoints (if applicable)
The following parameters will be measured during the baseline and post-evaluation assessment (T0 and T1) to obtain more insight in changes associated with dexterity on impairment, activity and participation levels: Semi-structured interview about user's experience

Other study parameters (if applicable)
In addition to the parameters measured during the evaluation measurements, during the course of the study the actual amount of use of the glove and/or exercises is logged by the iH system or registered by the participant.
Other parameters to be collected are descriptive subject characteristics (Appendix 1), which will be documented at the baseline measurement: Location of the stroke (size based on imaging (e.g. CT-scan), if it is present in the subjects status; only for stroke population)

Randomisation, blinding and treatment allocation
The patient population will be stratified by diagnosis. Then participants will be randomly assigned via a list of random numbers (randomisation list) to one of the three intervention groups to provide an equal number of participants in all groups. (block randomisation). The randomization procedure will take place after the baseline measurement.
In addition, the order of the functional tests with and without wearing the glove will be randomized within one session before the start of the functional hand function tests in both evaluation sessions. The numbers 1-10 will be distributed over 10 envelopes. For each participant, the researcher will take one envelope from these 10 envelopes to randomize the order of functional tests with and without the glove. If the researcher draws an even number, the participant will perform all functional tasks with the glove first during both evaluations. If the researcher draws an odd number, the participant will perform all functional tasks without the glove first during both evaluations.
The study cannot be blinded for the participants or researchers.

Study procedures
Each participant will have a baseline (T0) and post-training evaluation session (T1). The baseline measurement will consist of a short introduction and instruction about how to use the iH system, followed by several hand function tests with and without the use of the glove to assess the direct influence of the iH system before prolonged use. The post-training measurement follows the same procedure as the baseline measurement, with addition of assessment of user acceptance through several questionnaires. The complete list of procedures of the study is shown in Table 1

Jebsen-Taylor hand function test (JTHFT) (Appendix 2)
The JTHFT is a reliable and valid test to evaluate functional hand motor function in different patient groups and healthy people of various ages [30]. The test consists of 7 different unilateral hand skill tasks related to ADL: (1) writing a sentence of 24 characters (2) turning over 7.6-x 12.7-cm cards (3) picking up small, common objects (e.g., paper clips, coins and bottle caps) and move these to a box (4) stacking checkers (test of eye-hand coordination) (5) simulated feeding (e.g. teaspoon with beans) (6) picking up large empty cans (7) moving weighted (450 g) cans. The time of each different task will be recorded in seconds and the different times summed is the total score for the test [30,31].

Maximal handgrip strength
The maximal handgrip strength will be measured with a Jamar dynamometer [32,33]. Each participant will sit comfortably with the elbow of the most-affected arm close to their body, flexed 90 degrees, holding the dynamometer in the most-affected hand. The other parts of the body are not allowed to move or help to give more strength. The participant will squeeze the handgrip of the dynamometer maximally, which is maintained for 5 seconds. There will be three attempts and between the different attempts is at least 60 seconds rest. The best of the three attempts will count. This measurement will be done by the less-affected hand as well for reference purposes.

Handgrip endurance
Handgrip endurance will be measured in a static situation. In the static situation, the participants will squeeze the Jamar dynamometer maximally for 30 seconds. The formula for analysing fatigue in a static situation is last second / first second, to measure the change in power (N) in percentage [34]. The participant has one attempt for both conditions with and without the glove.

Maximal pinch strength
The maximal pinch strength will be assessed with a Jamar pinch Gauge dynamometer. The pinch strength will be measured between the index finger and the thumb and the ring finger and the thumb. The subject will be seated comfortably with the elbow close to their body, flexed 90 degrees and resting on a table. The subject will in all attempts grasp the pinch dynamometer with the distal segment and ventral side of the thumb and finger. In all attempts, the subject will squeeze in the pinch dynamometer maximally with the two fingers for at least 5 seconds.
The other fingers are not allowed to give any support. The subject will get 3 attempts for each test and the best one counts. Between all the attempts is at least 60 seconds rest.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises The BBT is a simple, reliable and valid measurement to measure manual dexterity of elderly people [35]. In the test, the participant grasps blocks with his or her most-affected hand and transfers these from one box to the other adjacent box. The maximum time for this measurement is one minute and the participant has to transfer as many blocks as possible, one at a time. At the end of the measurement, the number of transferred blocks is counted.

Motor Activity Log (MAL) (Appendix 4)
The MAL is a semi-structured questionnaire to explore the self-perceived amount of use and quality of movement of the affected arm and hand in stroke patients in ADL. This questionnaire consists of 26 activities and has excellent test-retest reliability for both scores of each activity

SF-36 questionnaire (Appendix 5)
The SF-36 is a 36 item questionnaire to assess health perception of people. It is a validated and reliable assessment for measuring health perception [39]. The questionnaire consists of multi-item dimensions about physical and mental well-being of the participant. The scores of the questionnaire will be converted to a 0 -100 scale, where a higher score indicates a better QoL [39,40].

System Usability Scale (SUS) (Appendix 6)
The SUS is a simple, valid and reliable questionnaire for systems' usability. It uses a 5-point Likert scale for 10 questions about ease of use and related issues. The answers can range from 'strongly disagree' till 'strongly agree'. The total score of the questions will be multiplied by 2.5, so that the maximum score is 100 [41].

Intrinsic Motivation Inventory (IMI) (Appendix 7)
The IMI questionnaire is a simple, easy to use, valid and reliable questionnaire to assess individuals' intrinsic motivation during any specific exercise activity [42][43][44]. The items of the IMI questionnaire will be scored by the participant on a 7-point Likert scale in the range from 'not at all true' till 'very true' [42].

Withdrawal of individual subjects
Subjects can leave the study at any time for any reason if they wish to do so without any consequences. The investigator can decide to withdraw a subject from the study for urgent medical reasons.

Specific criteria for withdrawal (if applicable)
A subject will be withdrawn if the subjects' health is affected or other adverse effects are encountered during the use of the device.

Replacement of individual subjects after withdrawal
If possible within the duration of the study, the subject will be replaced after withdrawal.

Follow-up of subjects withdrawn from treatment
There will be no follow-up for the subjects after withdrawal from the study.

Premature termination of the study
The study will be terminated prematurely if serious adverse events occur during the study procedures. In such situations, the subjects will be informed as quickly as possible by the accredited METC and laboratory manager.

Temporary halt for reasons of subject safety
In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the study if there is sufficient ground that continuation of the study will jeopardise subject health or safety. The sponsor will notify the accredited METC without undue delay of a temporary halt including the reason for such an action. The study will be suspended pending a further positive decision by the accredited METC. The investigator will take care that all subjects are kept informed.

Adverse events (AEs)
Adverse events are defined as any undesirable experience occurring to a subject during the study, whether or not considered related to the use of the iH system. All adverse events reported spontaneously by the subject or observed by the investigator or his staff will be recorded.

Serious adverse events (SAEs)
A serious adverse event is any untoward medical occurrence or effect that results in death; is life threatening (at the time of the event); requires hospitalisation or prolongation of existing inpatients' hospitalisation; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or any other important medical event that did not result in any of the outcomes listed above due to medical or surgical intervention but could have been based upon appropriate judgement by the investigator.
An elective hospital admission will not be considered as a serious adverse event.
The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within 7 days of first knowledge for SAEs that result in death or are life threatening followed by a period of maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported within a period of maximum 15 days after the sponsor has first knowledge of the serious adverse events.

Suspected unexpected serious adverse reactions (SUSARs)
This chapter is not applicable because the iH system is not an investigational medicinal product.

Annual safety report
This chapter is not applicable because the iH system is not an investigational medicinal product.

Follow-up of adverse events
All AEs will be followed until they have abated, or until a stable situation has been reached. Depending on the event, follow up may require additional tests or medical procedures as indicated, and/or referral to the general physician or a medical specialist.
SAEs need to be reported till end of study within the Netherlands, as defined in the protocol.

[Data Safety Monitoring Board (DSMB) / Safety Committee]
Not applicable.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

STATISTICAL ANALYSIS
The data of the outcome measures will be analysed using IBM SPSS Statistics version 23.0.
All data will be checked for normal distribution by visual inspection of the q-q plot, the box plot, histogram plot and by the Shapiro-Wilks test, prior to the statistical analyses of the various outcome measures. Descriptive statistics will be used for all outcome measures, using mean ± standard deviation (SD) or median and interquartile range (IQR) as applicable. The overall level of significance will be set at p< 0.05.

Primary study parameter(s) and secondary study parameter(s)
A paired sample t-test or its non-parametric equivalent, the Wilcoxon signed rank test, will be executed to establish the direct/orthotic effect of the iH system for the various hand function outcome measures separately (JTHFT, handgrip strength, BBT, MAL).
In order to assess the effect of the intervention and the differences between the three intervention groups, an one-way ANOVA or the Friedman Test (non-parametric test) will be established for the different outcome measures separately. If a significant difference is found for parametric variables, multiple comparisons are performed with a Bonferroni correction. A Wilcoxon signed rank test for multiple comparisons will be performed using an adjusted Pvalue of 0.017, if a significant difference for non-parametric variables is found.
In addition, correlation analyses will be used to identify correlations between motivation, usability, actual amount of use and outcome measures for functionality of the hands. The correlation analyses will be established with the parametric Pearson's correlation coefficient or the non-parametric Spearman's correlation coefficient.

Other study parameters
Descriptive statistics will be used to show the mean ± SD or median and interquartile ranges of the relevant subjects' characteristics.

Interim analysis (if applicable)
Not applicable.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

Recruitment and consent
The elderly population will be selected by the researchers of RRD or NFE based on inclusion and exclusion criteria. The patient population will be selected by a rehabilitation physician and/or therapist. Potential candidates will be asked if they are interested in participation. When expressing interest in participation (to the researcher or rehabilitation physician), subjects will be provided with written and verbal information about the study by the researchers. The subject has one week to consider their decision for involvement in the study. If the subject decides to participate in the study, the subject has to sign the attached informed consent indicating voluntary participation in this study and satisfactory information provision about all aspects of the study.

Objection by minors or incapacitated subjects (if applicable)
Not applicable.

Benefits and risks assessment, group relatedness
The iH system may have a beneficial effect on hand function, by directly improving functional task performance or by using it as a training tool. It might be possible that the functional use of the hand improves, allowing people to be more active in ADL and to maintain or improve their health status. However, the exact benefit cannot be predicted, because this is the topic of the current research.
The risks for the subjects are limited to a minimum. The iH system is a device that facilitates hand grip and opening as initiated by the user him/herself. It provides support only when necessary based on voluntary, active initiation by the person him/herself. Furthermore, the iH system is a so-called soft-robotics device, constructed from soft materials that are comfortable to wear and compliant with human movement. All movements conducted during the study will consist of hand movements that normally occur in ADL and within the abilities of each individual. Additionally, all the evaluation measurements used in these studies are noninvasive and involve no risks for the subjects.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

Compensation for injury
The sponsor/investigator has a liability insurance which is in accordance with article 7 of the WMO.
The sponsor (also) has an insurance which is in accordance with the legal requirements in the Netherlands (Article 7 WMO). This insurance provides cover for damage to research subjects through injury or death caused by the study.
The insurance applies to the damage that becomes apparent during the study or within 4 years after the end of the study.

Incentives (if applicable)
Subjects can receive compensation for travel costs. clinical trials and laboratory test will be numerically coded. The information that is concealed by the numeric code is only accessible by the investigators. If necessary, the subject can be linked to the data by a subject identification code list which is safeguarded by the investigators.
All data will be stored in coded form for the next 15 years. When data is transferred between the project partners, this will concern coded data only. Furthermore, sensitive data will be protected with an encryption. The researchers can use the data for research purposes, such as presentations in a scientific context and conferences without the names and identities of the subjects.

Monitoring and Quality Assurance
Not applicable.

Amendments
Amendments are changes made to the research after a favourable opinion by the accredited METC has been given. All amendments will be notified to the METC that gave a favourable opinion.
Non-substantial amendments will not be notified to the accredited METC and the competent authority (CA), but will be recorded and filed by the sponsor. Examples of non-substantial amendments are typing errors and administrative changes like changes in names, telephone numbers and other contact details of involved persons mentioned in the submitted study documentation.

Annual progress report
The sponsor/investigator will submit a summary of the progress of the trial to the accredited METC once a year. Information will be provided on the date of inclusion of the first subject, numbers of subjects included and numbers of subjects that have completed

Temporary halt and (prematurely) end of study report
The investigator/sponsor will notify the accredited METC of the end of the study within a period of 8 weeks. The end of the study is defined as the last patient's last visit.
The sponsor will notify the METC immediately of a temporary halt of the study, including the reason of such an action.
In case the study is ended prematurely, the sponsor will notify the accredited METC within 15 days, including the reasons for the premature termination.
Within one year after the end of the study, the investigator/sponsor will submit a final study report with the results of the study, including any publications/abstracts of the study, to the accredited METC.

Public disclosure and publication policy
There are no restrictions between sponsor and investigators concerning public disclosure and publication of the research data.

NL56746.044.16
A robotic glove that supports ADL and therapeutic exercises

STRUCTURED RISK ANALYSIS
Potential risks of the iH system prototype to be used in these research studies were identified and evaluated as described in Figure 3. Risk assessment of the iH system operating in in both orthotic mode and therapeutic mode are covered in the IMDD and its appendices in detail (see Figure 3).

Figure 3. Overview of the risk management documents for the iH system
Risk causes and risk control measures have been reviewed and evaluated in the IMDD and associated documents. The conclusion is, given the intended use of the device, that the overall residual risk is acceptable. There were no identified unacceptable residual risks that may occur in connection with and application of the iH system prototype in this proposed research study.
Risk management will continue during the development and testing of the iH system prototype.
Any feedback from usage of the device during the usability test will be immediately considered in the risk management process.

iH system (therapeutic mode)
Risk assessment of the iH TS components and its connection to the iH AS.
It mainly covers the risks of the iH system when used in therapeutic mode.

iH AS (orthotic mode)
Risk assessment of the iH AS and its connection to the iH TS. It also covers the risks of the iH system when used in orthotic mode. This document fills the gaps in functionality and design between the iH AS and

Jebsen-Taylor Hand Function test
Materials: the JTHFT-kit, stopwatch, table and chair (with backside, preferably without armrests).
In the iH project, the JTHFT test will measure a) fine motor skills; (b) weighted functional tasks; and (c) non-weighted functional tasks [45]. The JTHFT consist of the following 7 tasks: Writing a short sentence (24 letters, 3rd grade reading difficulty) Turning over a 3x5 inch card Picking up small common objects (e.g., paper clips, coins and bottle caps) Simulated feeding (e.g. teaspoon with beans) Stacking checkers (test of eye-hand coordination) Picking up large light cans (e.g. empty cans) Picking up large heavy cans (450 g) The JTHFT tasks are performed according to the instructions of Jebsen et al. 1969 [45]. The subject sits close to the table and the trunk must remain in contact with the back of the chair throughout testing. The distance between the subject and the activity should be a comfortable distance.
The time of each different task will be recorded in seconds and all times summed is the total score for the test. The participant will start after the researcher count up to 3 and in the meantime the researcher starts the stopwatch. The researcher stops the stopwatch when the subject finished the activity.

Semi-structured interview about user experience -Assistive group
We strive to develop products that meet your needs. Therefore we highly appreciate that you agreed to participate in the testing of the ironHand system. With the following questions we would like to receive your feedback about the usage and effect of the ironHand system that you tested during the last weeks. Your participation helps us to continuously improve our products within the clinical environment. Thank you very much for your feedback!

Semi-structured interview about user experience -therapeutic group
We strive to develop products that meet your needs. Therefore we highly appreciate that you agreed to participate in the testing of the ironHand system. With the following questions we would like to receive your feedback about the usage and effect of the ironHand system that you tested during the last weeks. Your participation helps us to continuously improve our products within the clinical environment. Thank you very much for your feedback!

14)
What do you think about the ease of use of the ironHand therapeutic system?  ..