Usability and Effectiveness of a Novel Bilateral Upper Limb Training Device for Stroke Patients With Hemiparesis: A Preliminary Study
Phase: NA
Conditions: The Effectiveness of Novel Rehabilitation Device on Upper Limb Impairment Among Patients With Stroke
Sponsor: Chang Gung Memorial Hospital

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
 
An Assessment of the Usability of a Novel Upper Limb 
Rehabilitation Device in Patients with Stroke 
 
VERSION NO. 1 
 DATES (2023/07/01) 
 
 
 
Liu, Kuo-Cheng 
New Taipei Municipal Tucheng Hospital 
 
 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
 
Table of Contents 
 
Section 
Page 
1. Synopsis ...................................................................................................................................1 
2. Introduction and Rationale ............................................................................................................. 
3. Objectives and Endpoints .......................................................................................................... 
3.1. Study Objectives ..................................................................................................................  
3.2. Study endpoints ...................................................................................................................  
4. Study Design.............................................................................................................................. 
4.1. Overall Design (Flow Chart) ...............................................................................................  
4.2. Number of Patients ...............................................................................................................  
4.3. Schedule of Activities (Time-Event scheme) ......................................................................  
5. Study Population ........................................................................................................................ 
5.1. Inclusion Criteria ..................................................................................................................  
5.2. Exclusion Criteria ................................................................................................................  
5.3. Withdrawal criteria .......................................................................................................................... 
6. Treatments ................................................................................................................................. 
6.1. Treatments Administration ..................................................................................................  
6.2. Concomitant Therapy ......................................................................................................  
7. Efficacy Assessments ............................................................................................................ 
8. Safety Assessments 
9. Adverse Event reporting 
9.1. Definition and reports of Adverse Events........................................................................  
9.2. Adverse event follow-up ..................................................................................................  
10. Criteria for the termination of the trials 
11. Statistical Considerations 
11.1. Sample Size Determination ............................................................................................ 
11.2. Planned Statistical methods of analysis .......................................................................... 
11.2.1. Efficacy analyses ...................................................................................................... 
11.2.2. Safety analyses ......................................................................................................... 
11.2.3. Additional analyses .................................................................................................. 
11.2.4. The level of significance .......................................................................................... 
11.2.5. Analysis Population .................................................................................................. 
12. Direct access to source data/documents 
13. Ethical considerations 
14. Data handling and keeping 
15. Financing and Insurance 
16. References.............................................................................................................................. 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
1. Synopsis 
 
 
Protocol Title： 
Usability Analysis of a Novel Bilateral Upper Limb Rehabilitation Device in Post-Stroke 
Hemiplegia 
Study Objectives： 
    Post-stroke patients commonly experience upper limb impairment, with approximately 85% 
affected during the acute phase and 40% continuing to experience dysfunction in the chronic 
phase. Functional upper limb use is essential for daily living and social participation. However, 
current rehabilitation often requires external assistance or costly robotic devices, which limits 
accessibility. 
    This study proposes a novel, non-powered mechanical bilateral upper limb rehabilitation 
system that is easy to don and operate, reduces assistance needs, and allows patients to 
independently perform rehabilitation exercises. The device aims to improve treatment 
accessibility and efficiency while promoting upper limb recovery. The study consists of three 
phases: Prototype adjustment; Device fitting and training assessment; Usability and satisfaction 
evaluation. 
 
Investigational product(s)： 
A non-powered, mechanically structured bilateral rehabilitation device designed to facilitate 
independent upper limb training and enhance rehabilitation accessibility. 
Development Phase：⃞ I   ⃞II    ⃞III     ⃞IV    ⃞other______   Not applicable  
 
    Study Design： 
1. ■ Experimental Group：Bilateral upper limb training with the novel device + conventional 
occupational therapy 
■ Control Group ：  □  Placebo  
□ Study Drug  (Name、Dose、Usage)  __________________ 
■  Other：Upper limb functional training + conventional occupational 
therapy 
2. Blinding：■ Open  □ Evaluator-blind  □ Single-blind(patient)  □ Double-blind(patient+PI)   
□ Double Dummy   □ Other ______________ 
3.  Randomization:  ■ Yes   □ No 
4. ■ Parallel design   □ Crossover design   □ Other ____________   □ Not applicable 
5.  Treatment Period：1 month   □ Not applicable 
  6.  Study Period: 1 years (2023/08/01-2024/07/31) 
6. Dose adjustment：□ Mandatory     □ Selectively       □ No        ■ Not applicable 
7. Study location：■ Single □ Multi-center  □  Global  
Endpoints (Outcome measure)： 
Primary endpoint:  
⚫ Fugl-Meyer Assessment for Upper Extremities (FMA-UE) 
Secondary endpoint: 
⚫ Brunnstrom stage  

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
⚫ Spasticity: Modified Ashworth Scale (MAS) 
⚫ Usability: System Usability Scale (SUS) 
⚫ Test-retest reliability of repeated training sessions 
⚫ User satisfaction: Satisfaction questionnaire 
Inclusion/Exclusion Criteria： 
Inclusion Criteria 
⚫ Stroke onset ≤12 months 
⚫ Age 18–70 years 
⚫ Stable physiological and neurological status for ≥72 hours 
⚫ Able to follow at least two-step commands 
⚫ Written informed consent obtained 
⚫ Unilateral upper limb hemiplegia 
⚫ Brunnstrom stage > I (proximal UE) 
⚫ MAS < 3 (affected UE) 
 
Exclusion Criteria 
⚫ Musculoskeletal impairments preventing device use 
⚫ Active, non-healed dermatological lesions 
⚫  
Study Procedures： 
The study employs a novel non-powered bi-manual rehabilitation device based on 
mechanical transmission principles, specifically designed for upper limb training in post-stroke 
patients. The device operates through a linear guide rail system that enables the unaffected limb 
to drive the movement of the affected limb along a mirrored trajectory. This bilateral training 
approach allows simultaneous motion of both upper limbs, enabling the unaffected side to assist 
in generating active movement in the hemiplegic arm. 
Key features of the device include: (1) bilateral limb synchronization, whereby movement 
of the unaffected upper limb facilitates motion of the affected limb; (2) a purely mechanical, 
power-free transmission system utilizing linear rail sliders; and (3) training guided along 
specific two-dimensional movement trajectories. The device is expected to maintain or improve 
joint range of motion (ROM), reduce spasticity as measured by the Modified Ashworth Scale 
(MAS), and promote neuroplasticity in the affected neural pathways. 
The structural design centers around a central transmission module that links the motion of 
the two limbs via linear rails to minimize mechanical resistance. The forearm is secured using 
an end-effector mechanism, and the device allows for directional movement through 
longitudinal and lateral rail systems. Different training trajectories can be achieved by varying 
the patient’s seated position, supporting functional training across a range of upper limb motion 
patterns.    

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
Prior to training, the rehabilitation physician evaluates the affected shoulder and elbow 
joints using the Brunnstrom Recovery Stage, Fugl-Meyer Assessment for Upper Extremities 
(FMA-UE), and MAS. Based on MAS scores, patients are stratified into two groups: those with 
MAS <1 and those with MAS ≥1. Participants are then randomly assigned to either the 
experimental group—receiving bilateral upper limb training with the device combined with 
conventional occupational therapy—or the control group—receiving only conventional upper 
limb occupational therapy. 
For the experimental group, patients are instructed on how to use the device, and a 
therapist provides assistance during operation. After the initial session, patients repeat the same 
training one week later to assess test-retest reliability. Training includes two components: (1) 
single-joint exercises targeting either the shoulder or elbow, with 20 repetitions per joint for 5 
sets, each set separated by a 30-second rest; and (2) dual-joint exercises involving functional 
movement along rectangular and triangular paths, also conducted in 5 sets of 20 repetitions 
with similar rest intervals. 
Control group training involves conventional functional tasks targeting the affected limb, 
such as box-pushing (standing or seated), alternating push-pull activities, and use of a hand-
cycle. Both groups train for 30 minutes per day, five days a week, for a total of 15 sessions over 
three weeks. All participants continue their routine rehabilitation treatments throughout the 
study.At the conclusion of the three-week intervention, the rehabilitation physician reassesses 
Brunnstrom stage, FMA-UE, and MAS to evaluate functional changes in the affected upper 
limb. 
To assess usability and user satisfaction, both patients and therapists complete the System 
Usability Scale (SUS) and a satisfaction questionnaire following the training period. The SUS 
consists of 10 items rated on a five-point Likert scale ranging from "strongly disagree" to 
"strongly agree." Odd-numbered items are positively worded, while even-numbered items are 
negatively worded. Scoring involves subtracting 1 from positive item scores and subtracting the 
original score from 5 for negative items; the total is then multiplied by 2.5 to yield a final SUS 
score out of 100. 
The satisfaction questionnaire assesses five domains—overall satisfaction, comfort, ease 
of donning the device, perceived improvement in ROM, and rehabilitative assistance—using a 
five-point Likert-type scale ranging from 1 (very poor) to 5 (very good). 
         
1. Concomitant Treatments：  ■Not applicable 
1. Concomitant Therapy： 
      2. Prohibited Therapy： 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
Statistical Methods： 
1. Main study Hypothesis： □ Equality  ■ Superiority  □ Non-inferiority  
   ⃞ Equivalence   □ Other ________ 
2. Estimated Sample Size： 
The planned enrollment for this trial includes 60 stroke patients, with an overall evaluable 
sample size of 70 individuals. This estimation is based on the recommendation by Lewis and 
Sauro (2009), who suggest that a minimum of 12 participants is appropriate for usability 
assessments. In the present study, participants will be categorized into four subgroups based on 
MAS scores (either <1 or ≥1) and intervention type (experimental or control). To ensure that 
each subgroup has at least 12 participants, a minimum of 48 participants is required (12 per 
subgroup). An additional 25% (12 participants) will be recruited to account for potential 
dropout, bringing the total number of stroke patients to be enrolled to 60. Our center has the 
capacity to recruit and evaluate all 70 participants. 
In addition to prospective participants, retrospective data from 60 stroke patients will be 
included for analysis. Furthermore, a total of 10 individuals—including trained therapists and 
healthy subjects (such as caregivers or family members who have received prior instruction)—
will be included to assess usability and support the study’s broader evaluation framework. 
3. Efficacy assessment group：  □ Intent-to-treat (ITT)   ■ Per-Protocol (PP)   
                                                 □ Other ________ 
4. Interim analysis：  ■ Yes    □ No 
5. Statistical methods： 
Continuous variables will be presented as means with standard deviations, while 
categorical variables will be expressed as proportions. Independent t-tests will be used to 
compare continuous variables between groups, and Pearson’s chi-square test will be applied 
for categorical data. One-way analysis of variance (ANOVA) will be employed to assess 
differences across multiple groups. All statistical analyses will be conducted using the 
Statistical Package for the Social Sciences (SPSS). A p-value of less than 0.05 will be 
considered statistically significant. 
 
6. Handling of Missing Data： 
Only cases with complete datasets will be included in the analysis. Incomplete records will 
be excluded from statistical evaluation to maintain data integrity. 
 
 
2. Introduction and Rationale 
2.1 Investigational product(s) 
A non-powered, mechanically structured bilateral rehabilitation device designed to 
facilitate independent upper limb training and enhance rehabilitation accessibility. 
2.2 Animal and preclinical study data 
Not Applicable 
 
2.3 Clinical data 
Not Applicable 
 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
2.4 Risks / benefits Assessment 
During the operation of the equipment, there may be friction and shear effects on the skin, 
leading to potential skin lesion. Therefore, before conducting rehabilitation programs with 
the Synslai device, the skin that will touch the device will be covered with a bandage to avoid 
possible skin damage. Furthermore, risks are held to a minimum due to anonymous coding 
and keeping all data confidential with no identification to specific participants. No undue 
stress or uneven medical managements is anticipated as a result of patient's participation. 
Benefits for the participants is to be able to receive more types and longer time period of 
post-stroke rehabilitation programs for upper limbs paralysis. It facilitates the functional 
recovery of post-stroke hemiplegia. 
 
2.5 Regulatory 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board, and according to Good Clinical Practice standards.  No deviation from the 
protocol will be implemented without the prior review and approval of the IRB except where 
it may be necessary to eliminate an immediate hazard to a research subject.  In such case, the 
deviation will be reported to the IRB as soon as possible. 
 
3.  Objectives and Endpoints 
3.1 Study Objectives:  
Current rehabilitation strategies for post-stroke upper limb hemiparesis primarily rely on 
conventional functional training. However, stroke patients often encounter significant 
barriers to performing such exercises due to muscle weakness, increased muscle tone, and 
impaired neuromuscular coordination, which frequently necessitate additional physical 
assistance. While certain rehabilitation devices can help reduce this burden, their high cost 
limits accessibility and widespread clinical use. To address these challenges, this study 
proposes a novel bilateral upper limb rehabilitation training program incorporating a non-
powered mechanical device. The device is designed with a passive mechanical structure to 
significantly reduce production and operational costs, while simultaneously minimizing the 
need for external assistance during training. By combining affordability with functional 
utility, this approach aims to enhance rehabilitation accessibility and promote upper limb 
functional recovery in patients with post-stroke hemiplegia. 
 
3.2 Study endpoints: 
3.2.1 Primary endpoint: 
Fugl-Meyer Assessment for Upper Extremities (FMA-UE) 
3.2.2 Secondary endpoints: 
 
Brunnstrom stage  
 
Spasticity: Modified Ashworth Scale (MAS) 
 
Usability: System Usability Scale (SUS) 
 
Test-retest reliability of repeated training sessions 
 
User satisfaction: Satisfaction questionnaire 
4. Study Design 
4.1 Overall Design 
The study employs a novel non-powered bi-manual rehabilitation device based on 
mechanical transmission principles, specifically designed for upper limb training in post-stroke 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
patients. The device operates through a linear guide rail system that enables the unaffected limb 
to drive the movement of the affected limb along a mirrored trajectory. This bilateral training 
approach allows simultaneous motion of both upper limbs, enabling the unaffected side to assist 
in generating active movement in the hemiplegic arm. 
Key features of the device include: (1) bilateral limb synchronization, whereby movement 
of the unaffected upper limb facilitates motion of the affected limb; (2) a purely mechanical, 
power-free transmission system utilizing linear rail sliders; and (3) training guided along 
specific two-dimensional movement trajectories. The device is expected to maintain or improve 
joint range of motion (ROM), reduce spasticity as measured by the Modified Ashworth Scale 
(MAS), and promote neuroplasticity in the affected neural pathways. 
The structural design centers around a central transmission module that links the motion of 
the two limbs via linear rails to minimize mechanical resistance. The forearm is secured using 
an end-effector mechanism, and the device allows for directional movement through 
longitudinal and lateral rail systems. Different training trajectories can be achieved by varying 
the patient’s seated position, supporting functional training across a range of upper limb motion 
patterns.              
Prior to training, the rehabilitation physician evaluates the affected shoulder and elbow 
joints using the Brunnstrom Recovery Stage, Fugl-Meyer Assessment for Upper Extremities 
(FMA-UE), and MAS. Based on MAS scores, patients are stratified into two groups: those with 
MAS <1 and those with MAS ≥1. Participants are then randomly assigned to either the 
experimental group—receiving bilateral upper limb training with the device combined with 
conventional occupational therapy—or the control group—receiving only conventional upper 
limb occupational therapy. 
For the experimental group, patients are instructed on how to use the device, and a 
therapist provides assistance during operation. After the initial session, patients repeat the same 
training one week later to assess test-retest reliability. Training includes two components: (1) 
single-joint exercises targeting either the shoulder or elbow, with 20 repetitions per joint for 5 
sets, each set separated by a 30-second rest; and (2) dual-joint exercises involving functional 
movement along rectangular and triangular paths, also conducted in 5 sets of 20 repetitions with 
similar rest intervals. 
Control group training involves conventional functional tasks targeting the affected limb, 
such as box-pushing (standing or seated), alternating push-pull activities, and use of a hand-
cycle. Both groups train for 30 minutes per day, five days a week, for a total of 15 sessions over 
three weeks. All participants continue their routine rehabilitation treatments throughout the 
study.At the conclusion of the three-week intervention, the rehabilitation physician reassesses 
Brunnstrom stage, FMA-UE, and MAS to evaluate functional changes in the affected upper 
limb. 
To assess usability and user satisfaction, both patients and therapists complete the System 
Usability Scale (SUS) and a satisfaction questionnaire following the training period. The SUS 
consists of 10 items rated on a five-point Likert scale ranging from "strongly disagree" to 
"strongly agree." Odd-numbered items are positively worded, while even-numbered items are 
negatively worded. Scoring involves subtracting 1 from positive item scores and subtracting the 
original score from 5 for negative items; the total is then multiplied by 2.5 to yield a final SUS 
score out of 100. 
The satisfaction questionnaire assesses five domains—overall satisfaction, comfort, ease of 
donning the device, perceived improvement in ROM, and rehabilitative assistance—using a 

Protocol:  202301097A3                                                                                                                     Version: 1 
                                                                                                                                                             Date: 2023/07/03 
five-point Likert-type scale ranging from 1 (very poor) to 5 (very good). 
 
Flow Chart： 
 
 
 
4.2 Number of Patients 
The planned enrollment for this trial includes 60 stroke patients, with an overall 
evaluable sample size of 70 individuals. This estimation is based on the recommendation by 
Lewis and Sauro (2009), who suggest that a minimum of 12 participants is appropriate for 
usability assessments. In the present study, participants will be categorized into four 
subgroups based on MAS scores (either <1 or ≥1) and intervention type (experimental or 
control). To ensure that each subgroup has at least 12 participants, a minimum of 48 
participants is required (12 per subgroup). An additional 25% (12 participants) will be 
recruited to account for potential dropout, bringing the total number of stroke patients to be 
enrolled to 60. Our center has the capacity to recruit and evaluate all 70 participants. 
In addition to prospective participants, retrospective data from 60 stroke patients will be 
included for analysis. Furthermore, a total of 10 individuals—including trained therapists and 
healthy subjects (such as caregivers or family members who have received prior 
instruction)—will be included to assess usability and support the study’s broader evaluation 
framework.

 
10 
 
4.3 Schedule of Activities 
 
Time-Event scheme: 
  
Phase  
Recruitment  Pre-treatment 
Assessment 
Allocation 
Rehabilitation 
programs 
Post-treatment 
Assessment 
Evaluation  
 
 
 
 
 
Rehabilitation ward /  
Outpatient department 
V 
 
 
 
 
Screening /Administration 
 
 
 
 
 
Inclusion / Exclusion criteria  
V 
V 
 
 
 
Patient profile 
V 
V 
 
 
 
Assessment 
 
 
 
 
 
Brunnstrom stage 
 
V 
 
 
V 
Fugl-Meyer Assessment-Upper 
Extremities (FMA-UE) 
 
V 
 
 
V 
Modified Ashworth scale (MAS) 
 
V 
 
 
V 
Questionnaire 
 
 
 
 
 
System Usability Scale (SUS) 
questionnaire 
 
 
 
 
V 
Satisfaction questionnaire 
 
 
 
 
V 
 
 
 

 
11 
 
5. Study Population 
 
5.1 Inclusion Criteria 
⚫ Stroke onset ≤12 months 
⚫ Age 18–70 years 
⚫ Stable physiological and neurological status for ≥72 hours 
⚫ Able to follow at least two-step commands 
⚫ Written informed consent obtained 
⚫ Unilateral upper limb hemiplegia 
⚫ Brunnstrom stage > I (proximal UE) 
⚫ MAS < 3 (affected UE) 
 
5.2 Exclusion Criteria 
⚫ Musculoskeletal impairments preventing device use 
⚫ Active, non-healed dermatological lesions 
 
5.3 Withdrawal criteria 
Participants will be withdrawn from the study if they (1) become lost to follow-up, (2) develop 
new central nervous system lesions, or (3) experience decompensated systemic diseases that 
may compromise safety or study participation. 
6. Treatments 
 
6.1.Treatment Administration 
This study utilizes a non-powered bi-manual mechanical device for upper limb 
rehabilitation in post-stroke patients. The device operates via a linear rail transmission system 
that allows movements initiated by the unaffected upper limb to be mechanically transmitted to 
the affected limb, thereby facilitating bilateral synchronous motion along a defined trajectory 
within a single plane. This design enables joint mobilization without reliance on electric power, 
enhancing accessibility and reducing cost. 
Participants will be randomly assigned to either the control group, which will receive 
conventional occupational therapy alone, or the experimental group, which will receive a 
combination of device-assisted bilateral upper limb training and standard occupational therapy. 
For the experimental group, the rehabilitation protocol consists of: (1) isolated joint training for 
the shoulder and elbow, and (2) combined joint training involving functional tasks using 
rectangular and triangular trajectories. For both types of training, each task will be performed in 
5 sets of 20 repetitions, with a 30-second rest between sets. Training will be administered once 
daily for 30 minutes, five days per week, over a three-week period, totaling 15 sessions. All 
participants will continue to receive their usual standard care throughout the trial. 
6.2. Concomitant Therapy 
Not Applicable 
       
7. Efficacy Assessments 
 Primary endpoint: 
⚫ Fugl-Meyer Assessment for Upper Extremities (FMA-UE) 
Secondary endpoints: 
⚫ Brunnstrom stage  
⚫ Spasticity: Modified Ashworth Scale (MAS) 
⚫ Usability: System Usability Scale (SUS) 
⚫ Test-retest reliability of repeated training sessions 
⚫ User satisfaction: Satisfaction questionnaire 

 
12 
 
8. Safety Assessments 
Not Applicable 
 
9. Adverse event reporting 
Liu, Kuo-Cheng will report SAEs to the IRB of Chang Gung Medical Foundation according 
to the Serious Adverse Event Reporting Procedures and Guidelines as posted in the Clinical 
Trials Resource on the website of Chang Gung Medical Foundation IRB. SAE reports to the 
IRB should include the following information when calling the Medical Monitor: 
• Date and time of the SAE 
• Date and time of the SAE report 
• Name of reporter 
• Call back phone number 
• Affiliation/Institution conducting the study 
• Protocol number 
• Title of protocol 
• Description of the SAE, including attribution to drug and expectedness    
 
9.1 Definitions and reports of Adverse Events 
All adverse events that occur after the informed consent is signed (including run-in) must be 
recorded on the adverse event CRF (paper and/or electronic) whether or not related to study 
agent. AE Data Elements including: 
• AE reported date 
• AE Verbatim Term 
• CTCAE Term (v 5.0) 
• Event onset date and event ended date 
• Severity grade 
• Attribution to study agent (relatedness) 
• Whether or not the event was reported as a Serious Adverse Event (SAE) 
• Action taken with the study agent 
• Outcome of the event 
• Comments 
 
Identify the adverse event using the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0.  The CTCAE provides descriptive terminology and a grading scale for 
each adverse event listed. 
 
AEs will be assessed according to the CTCAE grade associated with the AE term.  AEs that 
do not have a corresponding CTCAE term will be assessed according to their impact on the 
participant’s ability to perform daily activities as follows: 
 
 
Grade 
Severity 
Description  
1 
Mild 
• 
Barely noticeable, does not influence functioning 
• 
Causing no limitations of usual activities 
2 
Moderate 
• 
Makes participant uncomfortable, influences functioning 
• 
Causing some limitations of usual activities 

 
13 
 
3 
Severe 
• 
Severe discomfort, treatment needed 
• 
Severe and undesirable, causing inability to carry out 
usual activities 
4 
Life threatening 
• 
Immediate risk of death 
• 
Life threatening or disabling 
5 
Fatal 
• 
Causes death of the participant 
 
The possibility that the adverse event is related to study drug will be classified as one of the 
following:  not related, unlikely, possible, probable, definite. 
  
DEFINITION of Serious Adverse Events: ICH Guideline E2A and GCP of Taiwan define 
serious adverse events as those events, occurring at any dose, which meet any of the 
following criteria: 
• Results in death 
• Is life threatening (Note: the term life-threatening refers to an event in which the 
patient was at risk of death at the time of the event; it does not refer to an event 
which hypothetically might have caused death if it were more severe). 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital abnormality/birth defect 
• Events that may not meet these criteria, but which the investigator finds very 
unusual and/or potentially serious, will also be reported in the same manner. 
 
9.2 Adverse event follow-up 
All AEs, including lab abnormalities that in the opinion of the investigator are clinically 
significant, will be followed according to good medical practices and documented as such. 
Site staff should send follow-up reports as requested when additional information is available.  
Additional information should be entered on the IRB of Chang Gung Medical Foundation of 
SAE form in the appropriate format.  Follow-up information should be sent to Chang Gung 
Medical Foundation IRB as soon as possible according to IRB’s Serious Adverse Event 
Reporting Procedures and Guidelines.  
 
10. Criteria for the termination of the trial 
(1) Enroll requested number of patients and complete the study 
(2) Relevant research has been published and could confirmed the hypothesis of this study 
 
11. Statistical Considerations 
11.1 Sample size Determination 
Based on the recommendations by Lewis and Sauro (2009), a minimum of 12 
participants per group is considered appropriate for usability testing. In this study, 
participants will be categorized into four subgroups based on muscle tone classification 
(MAS < 1 or MAS ≥ 1) and treatment allocation (experimental or control group), resulting in 
a minimum required sample size of 48 (12 participants per subgroup). To account for an 
anticipated dropout rate of approximately 25%, an additional 12 participants will be recruited, 
leading to a total target enrollment of 60 stroke patients. In addition, 10 trained healthy 
participants—including caregivers or family members—will be included for usability 
assessments and device operation training. The total number of evaluable subjects for the 
study will therefore be 70. 
11.2 Planned Statistical methods of analysis 

 
14 
 
Continuous variables will be presented as means and standard deviations, while 
categorical variables will be reported as frequencies and percentages. Independent sample t-
tests will be used to compare continuous variables between groups, and Pearson’s chi-square 
test will be used for comparisons of categorical variables. One-way analysis of variance 
(ANOVA) will be applied to assess differences among the multiple subgroups. All statistical 
analyses will be conducted using SPSS (Statistical Package for the Social Sciences). A p-
value of less than 0.05 will be considered indicative of statistical significance. 
11.2.1 Efficacy analysis 
Primary endpoint: 
⚫ Fugl-Meyer Assessment for Upper Extremities (FMA-UE) 
Secondary endpoints: 
⚫ Brunnstrom stage  
⚫ Spasticity: Modified Ashworth Scale (MAS) 
⚫ Usability: System Usability Scale (SUS) 
⚫ Test-retest reliability of repeated training sessions 
⚫ User satisfaction: Satisfaction questionnaire 
 
 
11.2.2 Safety analysis 
Not Applicable 
 
11.2.3 Additional analysis 
Not Applicable 
 
11.2.4 The level of significance 
A p-value less than 0.05 was considered significant and was denoted by alternative 
hypothesis and p-value more than 0.05 was denoted by null hypothesis. 
 
11.3 Analysis Population 
The analysis population of this study is the patient aged 18-70 years with the onset of stroke 
attack within 12 months, Brunnstrom stage of upper limb >1 and Modified Ashworth Scale 
of upper limb < 3. All the subjects should be able to understand and cooperate with the 
instructions from the therapists or caregivers.  
 
11.4 Procedure for accounting for missing, unused and spurious data 
The approach to the missing data is to simply omit those cases with the missing data and 
analyze the remaining data. 
 
11.5 Procedures for reporting any deviation(s) from the original statistical plan 
The collected data will not be used in the statistical analysis if the patients do not meet the 
inclusion criteria. For unused data, the trial investigators will analyze the possible factors 
which cause this specific condition and record them in the case report form. Any deviation 
from the original statistical design must have a reasonable explanation and be reported in the 
final report. 
 
12. Direct access to source data/documents 
Investigators permit IRB to access to the source data of experiment for trial-related monitoring, 

 
15 
 
audits and regulatory inspection. 
 
13. Ethical considerations 
This study will be conducted according to Taiwan and international standards of Good 
Clinical Practice for all studies. Applicable government regulations and Chang Gung Medical 
Foundation research policies and procedures will also be followed. 
 
This protocol and any amendments will be submitted to the Chang Gung Medical Foundation 
Institutional Review Board (IRB) for formal approval to conduct the study. The decision of 
the IRB concerning the conduct of the study will be made in writing to the investigator. 
 
All subjects for this study will be provided an informed consent describing this study and 
providing sufficient information for subjects to make an informed decision about their 
participation in this study. This informed consent will be submitted with the protocol for 
review and approval by the IRB. The formal consent of a subject, using the IRB-approved 
informed consent, will be obtained before that subject is submitted to any study procedure. 
The informed consent must be signed by the subject or legally acceptable surrogate, and the 
investigator-designated research professional obtaining the consent. 
 
14. Data handling and keeping 
Clinical data will be collected in Chang Gung Medical Foundation till the end of the study. 
The sequencing data will be stored in computers of laboratory with an electronic encryption. 
The clinical and source data can only be assessed by clinical doctors and investigators of the 
study. Each participant will be renamed with a number to keep the privacy of personal 
information. The clinical records for all participants, including protocol-specific case report 
forms, all source documentation (containing evidence to study eligibility, history and 
physical findings, laboratory data, and images), as well as IRB records and other regulatory 
documentation will be maintained at a minimum for 3 years in the well-protected device 
owned by the protocol lead investigator. 
 
15.  Financing and Insurance 
There will be no costs to subjects for any research related activities. All research-related costs 
will be paid by the Chang Gung Medical Foundation and the research team. The hospital and 
the trial lead investigator will be responsible for paying for injuries in case of accident. 
 
16. References 
 
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