Effects of Robot-assisted Therapy on Upper Limb and Cognitive Function in Patients With Stroke: Study Protocol of a Randomized Controlled Study

doi:10.21203/rs.3.rs-921595/v1

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Effects of Robot-assisted Therapy on Upper Limb and Cognitive Function in Patients With Stroke: Study Protocol of a Randomized Controlled Study

https://doi.org/10.21203/rs.3.rs-921595/v1

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Background

Impairments in upper limb function and cognitive ability are common complications among stroke patients, necessitating the development of novel and effective treatment options. The aim of this study was to explore the effects of robot-assisted therapy on improving upper limb and cognitive function in stroke patients.

Methods

This single-blinded, randomized controlled trial will include 86 acute and subacute stroke patients. Participants will be randomly assigned to receive either robot-assisted therapy or conventional therapy over a period of 4 weeks. In addition to comprehensive rehabilitation, the robot-assisted therapy group will receive a 30-minute Armguider robot-assisted therapy intervention 7 days a week. Patients will be assessed before and after the interventions. The outcome will be the Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Mini-Mental Status Examinations (MMSE), Trail Making Test (TMT), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), and Rey–Osterrieth Complex Figure Test (ROCFT).

Discussion

Our study is the first randomized controlled trial to explore the effects of robot-assisted therapy on upper limb function and cognition in acute and subacute stroke patients. Our findings will help to develop effective interventions for stroke patients with decreased cognitive function.

Trial Registration number

Chinese Clinical Trial Registry, ChiCTR2100050856. Registered on 5 September 2021.

Translational Medicine

Internal Medicine

Integrative & Complementary Medicine

robot-assisted therapy

upper limb function

cognition

stroke

Stroke is the second leading cause of death and the third leading cause of disability globally. [1, 2] There are approximately 3 million new stroke cases annually in China, which impose an enormous burden on family, society, and healthcare systems. [3–5] Motor and cognitive dysfunction are common complications following stroke and often coexist. [6] After a stroke, approximately 65% of patients live with upper limb dysfunction [3] and up to 75% exhibit cognitive impairment. [7–9] The prevalence of concurrent impairment ranges from 10–23%. Previous studies have shown that motor performance is associated with global cognition, memory, and executive function, and that cognitive dysfunction may attenuate mobility recovery. [10–12] Upper limb and cognitive dysfunction can significantly affect the quality of life, functional recovery process, and social participation among patients after stroke. [13–16] Thus, the identification of effective treatments for improving upper limb and cognitive function is of paramount importance.

There is currently a lack of high-quality evidence supporting the use of any specific intervention as a part of routine practice. Conventional rehabilitation approaches (e.g., manual therapy techniques, task-specific training, mental practice, and sensory intervention) [17] require patients to perform partial or full movements with the help or supervision of a therapist. Such interventions have been shown to be both time-consuming and labor-intensive. [18]

Robot-assisted therapy is a novel approach for the provision of a safe, repetitive, intensive, and quantitative rehabilitation intervention. [19] Since its initial deployment in clinical research, [20] there has been an increasing number of studies that have reported its potential to facilitate upper limb and cognitive function. [21–24] A recent review concluded that robot-assisted training can significantly improve upper limb motor impairment in stroke patients. [21] However, other studies have indicated that robot-assisted training is not significantly superior to usual care for the improvement of function after stroke. [22, 23] While previous research has mainly assessed the effects of robot-assisted training on motor performance, its effectiveness on cognition recovery has not been fully explored. The pilot study that assessed cognitive parameters reported improvements in cognitive impairment after robot-assisted training in patients with stroke; however, this study lacked a control group. [24] There has been an overall lack of compelling clinical evidence to substantiate the effects of robot-assisted therapy in improving upper limb and cognitive function. Therefore, we aim to compare the efficacy of robot-assisted therapy and conventional therapy in improving upper limb function and cognition among acute and subacute stroke patients in a randomized controlled trial.

Study design and participants

This study will utilize a single-blinded randomized controlled design. The study protocol is reported based on the SPIRIT reporting guidelines [25] and the figure 1 illustrates the planned flow of patients in the study. We will recruit patients from the First Rehabilitation Hospital of Shanghai. Recruitment strategies will include study promotion at each site, word of mouth, as well as the use of social media.

Patients will be included if they (a) are aged 18–80 years; (b) diagnosed with stroke by computed tomography or magnetic resonance imaging within 6 months following stroke onset; [26] (c) have a unilateral stroke for the first time; (d) have cognitive impairment (as determined via a Montreal Cognitive Assessment [MoCA] cut-off score of 26); [27,28] (e) have severe upper limb functional deficits (Fugl-Meyer Assessment for Upper Extremity [FMA-UE], 0–28); [24] and(f) are able to follow instructions. The exclusion criteria comprise the following: (a) severe visual, auditory, or speech impairments; (b) a history of epilepsy or serious heart, lung, liver, or kidney disease; (c) other diseases that affect the movement of the hemispheric upper limbs; (d) participation in robot-assisted training or other intervention programs in the past 3 months; and (e) inability to complete the entire intervention as required.

Experimental procedure

The trial will be conducted in an academic setting located in a research laboratory. At the first visit, patients and caregivers will be provided with an introduction of the study protocol, which will include the details of random assignment into either the robot-assisted therapy group or conventional therapy group. All patients will provide written informed consent prior to participation in the study. Participants’ demographic and clinical characteristics, as well as the study outcomes, will be assessed at baseline. After 4 weeks of intervention, the assessor will reevaluate the outcomes. The study protocol has been approved by the ethics committee of the First Rehabilitation Hospital of Shanghai. Table 1 shows the schedule of enrollment, assessments, and interventions.

Table 1. Schedule of enrollment, assessments, and interventions.

	Pre-intervention	4-week intervention	End of the intervention
TIME POINT	1 day	4 weeks	4 weeks +1 day
ENROLLMENT
Eligibility criteria	Î
Exclusion criteria	Î
Informed consent	Î
ASSESSMENTS
Demographic characteristics	Î
Fugl-Meyer Assessment for Upper Extremity	Î		Î
Mini-Mental Status Examinations	Î		Î
Trail Making Test	Î		Î
Auditory Verbal Learning Test	Î		Î
Digit Symbol Substitution Test	Î		Î
Rey–Osterrieth Complex Figure Test	Î		Î
Adverse events		Î	Î
ALLOCATION	Î
INTERVENTIONS
Intervention group (robot-assisted therapy + comprehensive rehabilitation)		Î
Control group (comprehensive rehabilitation)		Î

Î indicates the specific time point at which the corresponding measurement will

be performed.

Randomization and blinding

Patients meeting the inclusion criteria will undergo a baseline assessment. They will subsequently be randomly assigned (in a 1:1 ratio, using a computer-generated randomization sequence) into the robot-assisted therapy group or conventional therapy group. Allocation concealment will be ensured which a research assistant will conduct the randomization and not be participated in the intervention or assessment. Outcome assessors will be masked to group allocation and will not be involved in providing the interventions. Participants and therapists will not be masked to group allocation, due to the nature of the interventions.

Interventions

All patients will receive comprehensive rehabilitation therapy (45 minutes a day, 7 days a week over 4 weeks) that includes one-to-one physiotherapy and occupational therapy delivered by a certified physical and occupational therapist, respectively. In addition, the robot-assisted therapy group will use the Armguider upper-limb robotic (ZD MEDTECH, Shanghai, China), which is an intelligent rehabilitation training system specially designed for people with upper limb or cognitive dysfunction. It can provide passive, assistive, and active planar movements combined at the shoulder, elbow, and wrist joints. During treatment, patients are asked to perform both motor and cognitive tasks shown in a game scene that generates real-time auditory and visual feedback. The games that will be used are described below (Figure 2).

• Butterfly Capturing: Patients will be asked to control the net to capture a flying butterfly moving in different directions (this aims to assess visual-spatial ability and executive function).

• Playing Cards: A series of cards will be shown and then turned over. The patients will be asked to point out the cards with the same pattern (this aims to assess attention, scanning, memory, and delayed recall).

• Calculation: Patients will be asked to calculate the equations and move the correct answer to the designated position (this aims to assess computing ability).

• Fruit Ninja: Patients will be asked to observe the fruits that appear on the screen and cut them into sections while avoiding hitting obstacles (this aims to assess attention, graphic processing ability, response ability, and processing speed).

• Supermarket Shopping: Patients will be asked to buy the items on the list and pay the correct value of currency (this aims to assess cognitive ability, visual scanning, and selective attention).

• Little Bird Flying: Patients will be asked to control a bird passing through pillars of different heights and avoid hitting obstacles (this aims to assess visual scanning and judgment ability).

Participants will spend 5 minutes on each of the six games. When a game is completed, the system automatically and randomly switches to another game. The difficulty level of each game will be adjusted based on the patient’s ability and improvement. The experimental group will undergo the Armguider robot-assisted therapy intervention over a 4-week period, 30-min a day, 7 days a week. Patients will be monitored by their caregivers during the intervention period for potential adverse events.

A, Butterfly Capturing; B, Playing Cards; C, Calculation; D, Fruit Ninja; E, Supermarket Shopping; F, Little Bird Flying.

Outcome assessments

The variables in our study include demographic information and outcomes. Demographic information will be measured at baseline. The outcomes will be evaluated by two trained assessors at baseline and after the 4-week intervention period.

Demographic information

Patient demographic characteristics (age, sex, stroke type [hemorrhagic/ischemic], educational level, affected side, time after stroke, handedness) and history of disease will be collected by the assessors with a self-designed questionnaire.

Outcomes

1. Fugl-Meyer Assessment for Upper Extremity

The FMA-UE assesses upper limb impairment and consists of 33 items. Performance is scored on a three-point ordinal scale (0, 1, or 2), with a maximum score of 66 points. The items are summed to provide a final score, a higher score indicates minimal or no impairment. [29,30]

2. Mini-Mental Status Examinations

Global cognitive function will be assessed using the MMSE scale. MMSE is a single-page, 30-point test, which requires approximately 10 minutes to complete. It assesses different cognitive domains, including visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall and orientation, a higher score indicates better global cognitive function. [31]

3. Trail Making Test

Executive abilities will be evaluated through the TMT. The TMT includes parts A and B. In part A, patients are given a sheet of paper with circled numbers (from 1 to 25) and asked to draw lines to connect the numbers in ascending order, as quickly and accurately as possible. In part B, patients are again asked to connect the circles in ascending order, but are also instructed to alternate between numbers and letters. The time in seconds to complete each task is then analyzed. [32,33]

4. Auditory Verbal Learning Test

Memory will be measured using the AVLT. The assessor reads 12 two-character words randomly, and then the patients are required to recall the words. The test scores are calculated as follows: (1) AVLT Immediate Recall (AVLT-IR): the total of the correct recall words in the first three trials; (2) AVLT Short-term Delayed Recall (AVLT-SR): the sum of correct responses of free recall after short-term delayed (approximately 5 minutes); (3) AVLT Long-term Delayed Recall (AVLT-LR): the sum of correct responses of free recall after long-term delayed (approximately 20 minutes); (4) AVLT Category-cued Recall (AVLT-CR): the total of the correct answers under the category-cued recall condition; (5) AVLT Recognition Test (AVLT-REC): the total of the correct answers in the recognition test. [34]

5. Digit Symbol Substitution Test

Attention and processing speed will be assessed with the DSST. In this test, patients are given a sheet of paper with nine symbols and corresponding numbers from 1 to 9. Patients are instructed to write down each symbol under its corresponding number within 90 seconds; the number of correct answers are then scored. [35]

6. Rey–Osterrieth Complex Figure Test

Visuospatial abilities and visual memory will be evaluated using the ROCFT. In this assessment, patients are asked to complete a complicated geometrical figure, which is comprised of 18 elements. Each element is scored on a two-point scale (0, 1, or 2) based on accuracy and placement, with a higher score indicating a better performance. [36]

Statistical analysis

Sample size and power

The sample size is based on a comparison of the expected difference in the FMA-UE or MMSE scores between robot-assisted therapy and conventional therapy. Based on prior studies, [37,38] we determined that a sample size of 78 or 76 stroke patients will provide 80% power (at a two-tailed α-level of 0.05) for the detection of an effect size of 0.65 or 0.66, respectively, using G_*Power Version 3.1.9.4. Assuming a 10% attrition rate, we plan to recruit a total of 86 patients with acute or subacute stroke.

Statistical analysis

Categorical variables, including gender, stroke type (hemorrhagic and ischemic), affected side, handedness will be compared with Fisher’s exact test. The independent sample t test will be used if the comparison between the two groups conforms to the normal distribution and the Mann-Whitney U test for non-normal distribution. In addition, Data obtained before and after intervention which conform to the normal distribution will be compared by means of paired sample t test, and the Wilcoxon signed-rank test for non-normal distribution. All statistical analyses will be performed using SPSS version 25 (IBM Corp., Armonk, NY, USA), with the significance level set at p ≤ 0.05. Continuous variables and categorical variables will be presented as mean ± standard deviation or percentages, respectively.

Upper limb and cognitive dysfunction are among the top 10 research priorities related to life after stroke, based on a consensus from stroke survivors, caregivers, and health professionals. [39]Robot-assisted therapy is an emerging approach for the enhancement of the recovery process and provides safe, repetitive, high-intensity, and task-specific rehabilitation interventions. [40] The majorities of previous studies have been primarily focused on the effects of robot-assisted therapy on motor function, despite the importance of cognition. The present study is the first randomized controlled trial to explore the effects of robot-assisted therapy on upper limb function and cognition in acute and subacute stroke patients. Our findings will help to develop effective interventions for stroke patients with decreased cognitive function.

Trial status

The study registration number is ChiCTR2100050856 and currently in its recruitment phase.

FMA-UE: the Fugl-Meyer Assessment for Upper Extremity; MMSE: Mini-Mental Status Examinations; TMT: Trail Making Test; AVLT: Auditory Verbal Learning Test; AVLT-IR: AVLT Immediate Recall; AVLT-SR: AVLT Short-term Delayed Recall; AVLT-LR: AVLT Long-term Delayed Recall; AVLT-CR: AVLT Category-cued Recall; AVLT-REC: AVLT Recognition Test; DSST: Digit Symbol Substitution Test; ROCFT: Rey–Osterrieth Complex Figure Test; MoCA: Montreal Cognitive Assessment.

Ethics approval and consent to participate

The study protocol conforms to the Declaration of Helsinki and has been reviewed and approved by the First Rehabilitation Hospital of Shanghai. All patients will provide written consent prior to participation in the study.

Consent for publication

All authors have agreed to submit the protocol.

Availability of data and materials

Personal data will be stored at the First Rehabilitation Hospital of Shanghai. Investigators, research authorities, and ethics committees will be allowed to access patient health records. Any public reports on the results of this research will not disclose the patient’s personal identity. The results of this study will eventually be disseminated through peer-reviewed journals, medical conferences, rehabilitation forums, and presentations to stroke patients and their caregivers.

Competing interests

None declared

Funding

None

Author’s contributions

YW, MY, YT, LX, WT and JR were involved in the study concept and design, and drafted the manuscript. ZD will be responsible for randomization. XW, CG will be responsible for acquiring the data. YW, JR, WZ will be responsible for analysis and interpretation. All authors contributed to the article and approved the submitted version.

Acknowledgements

We would like to express our gratitude to all volunteers in this study.

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Editorial decision: Major revision
10 Dec, 2021
Reviews received at journal
09 Nov, 2021
Reviewers invited by journal
16 Oct, 2021
First submitted to journal
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Effects of Robot-assisted Therapy on Upper Limb and Cognitive Function in Patients With Stroke: Study Protocol of a Randomized Controlled Study

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