Robot-Assisted Training Versus Standard Training in Ischemic Stroke

Stroke Clinical Trial

Official title:

The Effect of Robot-Assisted Versus Standard Training on Motor Function Following Subacute Rehabilitation After Ischemic Stroke - a Randomised Controlled Trial Nested in a Prospective Cohort.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06273475
• Other study ID #: OUH RoboRehab
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2024
• Est. completion date: February 1, 2027

Study information

• Verified date: April 2024
• Source: Odense University Hospital
• Contact: Jon Skovgaard Jensen, Ph.d.-student
• Phone: +4530127595
• Email: jskovgaard[@]health.sdu.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this randomised controlled trial (RCT) nested in a prospective cohort, is to investigate the superior effect of late-phase robot-assisted versus standard training on motor function, physical function, fatigue, and quality of life in a moderately-to-severely impaired chronic stroke population following subacute rehabilitation.

The main hypothesis of the study is:

Robot-assisted training has a superior effect on motor function (Fugl-Meyer Lower Extremity Assessment; primary outcome), physical function, fatigue, and quality of life in moderately-to-severely impaired chronic stroke-affected individuals in comparison to standard training.

Description:

Background:

Stroke is the collective term for acute focal injuries to the central nervous system (CNS) caused by a disturbance in the blood circulation of the brain i.e., cerebral infarction (ischemic stroke) or intracerebral hemorrhage (hemorrhagic stroke). On an annual basis, 113,000 UK citizens and 12,000 Danish citizens are hospitalised following a stroke, and worldwide stroke is one of the leading causes of disability. Stroke-affected individuals may display residual impairments in motor, physical and cognitive functions along with mental fatigue and depression. Body weight unloading (BWU) has been suggested as a method of training for people with neurological disorders suffering from severe limitations in walking ability. BWU is the application of a vertical upwards force on the body centre of mass, thereby alleviating individuals of supporting their own body weight against gravity. However, the efficacy of BWU-based training is unclear. Therefore, the aim of the present study is to investigate the superior effect of late-phase robot-assisted versus standard training on motor function, physical function, fatigue, and quality of life in a moderately-to-severely impaired chronic stroke population following subacute rehabilitation.

Trial design overview:

Randomised, assessor-blinded, two-arm, multicentre trial. Participants will be recruited through Odense University Hospital, Herlev Gentofte Hospital and Rigshospitalet. Stroke-affected patients are recruited to the prospective cohort 3 months post-stroke. Stroke-affected individuals will be recruited to the RCT from the prospective cohort 6 months post-stroke and randomised 1:1 for robot-assisted training (intervention group) or standard training (active control group). Cohort participants not eligible and/or interested in participation in the RCT study will continue their participation in the prospective cohort.

The RCT study compares training with the robot-assisted body weight unloading to standard training without the robot. Training programs will be matched for total hours allocated to training and will consist of 2 sessions per week with a physiotherapist (one-on-one) and last 6 months (48 training sessions in total). Each session will last 60 minutes, 75 minutes and 90 minutes during the first, middle and last two months of the training program, respectively. Thus, INT and CON are matched for training time, but the effective training volume (resistance times repetitions) is not controlled.

Blinding:

The primary investigator will be blinded to allocation and will not participate in the randomisation, training or testing of participants. Statistical analysis will be performed on allocation codes. The test leader responsible for RCT-study testing will be blinded. It will not be possible to blind study participants and the physiotherapists conducting the training.

Randomisation Randomisation is performed internet-based using REDCap Randomise allocated 1:1. The randomisation takes place following pre-intervention testing at 6-months post-stroke. The study uses block randomisation in blocks of 2 and 4. Stratification is applied using the Modified Rankin Scale (3,4,5). The primary investigator is blinded with respect to the permuted blocking strategy. A data manager with no clinical involvement in the trial, prepares the randomisation sequence, and the allocation is concealed in a password-protected computer file.

Compliance

No study restrictions are imposed on potential regular 'outside-the-study' visits to physiotherapist or visits from occupational therapists. Acceptable adherence is defined as a completion of minimum 70% of scheduled sessions. Moreover, number/percent of completed training sessions and achievement of target intensity/volume will be registered in a training log by the physiotherapist.

Time points

Time points are reported as time since onset of stroke. The following time-points are therefore included in the present study: 3-, 6-, 12-, and 18-months post-stroke (corresponding to T3, T6, T12 and T18). Onset of stroke is indicated as T0.

Questionnaires are sent to the prospective cohort participants at T3, T6, T12, T18. RCT-outcomes will be assessed at pre-intervention (T6) and post-intervention (T12). Blood samples will be included at T3, T6, T12.

Sample Size

A priori sample size calculation was performed and resulted in a required sample size of 34 study participants. This was based on detecting a minimally clinically important between-group difference (MCID) of 6 points on the FM-LE scale and a standard deviation of 6 points at an α level of 5% and with a statistical power of 80%. Allowing for dropout the aim is to include 40 participants in total.

Statistical analysis

An assessor-blinded intention-to-treat (ITT) analysis will be performed on primary and secondary outcome measures (Primary Analysis). A full analysis data set will be created with two imputation techniques and sensitivity analysis will be performed to examine robustness of any statistically significant differences. The ITT analysis will employ a two-way analysis of variance (ANOVA) to analyse between-group differences in change-scores from pre- to post-intervention. A per protocol analysis (between-group differences in change-scores using ANOVA) will be included as a secondary analysis on participants demonstrating acceptable adherence (>70%).

Ethics:

The study was submitted to The Regional Committees on Health Research Ethics for Southern Denmark. The project approved the project on the 17th of January 2024.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 1, 2027
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion:

1. Ischemic apoplexia.

2. Chronic state (>6 months post-stroke).

3. Subacute rehabilitation terminated (subacute phase defined as until 6 months post-stroke).

4. Moderately-severely impaired:

1. Modified Rankin Scale Score 3-5.

2. Scandinavian Stroke Scale Leg Motor Function Score 0-4.

5. Approved by referring doctor

Exclusion:

1. Prior stroke, TIA, SAH

2. Severe fatigue making study completion improbable.

3. Cognitive deficits impeding study participation.

4. Inability to walk independently pre-stroke.

5. Recurrence of cardiovascular/cerebrovascular accidents.

6. Pre-existing neurological diseases or ongoing cancer treatment.

7. Refusing group allocation.

8. Concurrent participation in another clinical trial potentially interacting with the present trial.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Other:
• Robot-assisted Training
Gait training and functional strength training facilitated by body weight unloading robotic technology yielding a dynamic unloading force applied to the body centre of mass. Gait training will be conducted both on treadmill and overground. Functional strength training exercises include sit-to-stand, stair-walking, step-ups etc. The goal is to gradually reduce body weight unloading as participants progress through the intervention period.
• Standard Training
Gait training and functional strength training facilitated without the use of body weight unloading robotic technology, thereby only allowing manual assistance from physiotherapists. The goal of training is the same as in the intervention group, however no body weight unloading device will be implemented in the active control group.

Locations

Country	Name	City	State
Denmark	Rigshospitalet and Herlev Gentofte Hospital	Copenhagen
Denmark	Odense University Hospital	Odense

Sponsors (7)

Lead Sponsor	Collaborator
Odense University Hospital	Danish Association of the Physically Disabled, Herlev and Gentofte Hospital, Rigshospitalet, Denmark, Stanford University, Sygehus Lillebaelt, University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Contractile Muscle Power (between-group change)	The Nottingham Power Rig is a performance-based measurement used to measure the contractile muscle power of the leg extensors. Participants will sit in the power rig chair and push away a forceplate connected to a flywheel as hard and fast as possible.	Pre- and post-intervention (6 and 12 months post stroke)
Other	Modified Sit-to-Stand Test (between-group change)	This test is a modified version of the classic 5-times chair rise test. Participants will perform 5 sit-to-stand movements as fast as possible but will be provided with body weight unloading to facilitate a more appropriate movement intensity allowing them to finish within 60 second. Thus, this is a performance-based measurement.	Pre- and post-intervention (6 and 12 months post stroke)
Other	Blood Biomarkers (between-group change)	Blood samples will be drawn 3 months post stroke and pre- and post-intervention (6 and 12 months post-stroke). Samples will be analysed using single-molecule arrays (simoa) to determine blood concentrations of neurofilament light chain and glial fibrillary acidic protein and changes in peripheral blood mononuclear cells using flow cytometry	3, 6 and 12 months post stroke
Other	Modified Ashworth Scale (between-group change).	The Modified Ashworth Scale is clinical assessment of spasticity defined as velocity-dependent exaggeration of stretch reflexes. Change in muscle tone is assessed on a 6-point ordinal scale by moving the joints of the participants through full range of motion at a standardised velocity with ratings ranging from 0 (no increase in tone) to 4 (limb rigid in flexion and extension)	Pre- and post-intervention (6 and 12 months post stroke)
Other	Oxford Cognitive Screen (between-group change)	The Oxford Cognitive Screen (OCS) is a stroke-specific cognitive test with 5 domains: Attention and executive function, language, memory, number processing, and praxis. All tasks are scored individually and can be compared against normative data to determine impairments.	Pre- and post-intervention (6 and 12 months post stroke)
Other	Montreal Cognitive Assessment (between-group change)	The Montreal Cognitive Assessment (MoCA) is a dementia screening tool commonly used in clinical trials to screen for cognitive deficits following stroke. The MoCA tests the following cognitive domains and provides a total score from 0-30, where 30 indicates best possible cognitive function: visuospatial abilities, executive functions, short-term memory recall, attention, concentration, working memory, language, and orientation to time and space.	Pre- and post-intervention (6 and 12 months post stroke)
Other	Major Depression Inventory (between-group change)	The Major Depression Inventory is a dual function questionnaire (diagnostic tool or rating scale). In the present study it is used as a rating scale to indicate the degree of depression on a scale from 0 (no depression) to 50 (maximum depression).	Pre- and post-intervention (6 and 12 months post stroke)
Primary	Fugl-Meyer Lower Extremity Assessment of Motor Function	The primary outcome measure is the between-group difference in change score of Fugl-Meyer Lower Extremity Assessment (FM-LE) from pre- (T6) to post-intervention (T12). The FM-LE assesses motor function and has been recommended as a part of a core outcome set in stroke rehabilitation studies.	Pre- and post-intervention (6 and 12 months post stroke).
Secondary	Modified Rankin Scale Score (between-group change)	Global disability will be assessed using the Modified Rankin Scale, which classifies participants from 0-6 as 0) no symptoms, 1) no significant disability, 2) slight disability, 3) moderate disability, 4) moderate severe disability, 5) severe disability and 6) deceased.	3, 6, 12, and 18 months post stroke.
Secondary	Functional Ambulation Category (between-group change)	The Functional Ambulation Category is a clinical gait assessment scale used to distinguish 6 levels of walking ability based on required physical support. The categories are as follows: 0) Nonfunctional ambulation, 1) Ambulator - Dependent for Physical Assistance Level 2, 2) Ambulator - Dependent for Physical Assistance Level 1, 3) Ambulator - Dependent for Supervision, 4) Ambulator - Independent, Level surfaces only, 5) Ambulator - Independent.	Pre- and post-intervention (6 and 12 months post stroke)
Secondary	Berg Balance Scale (between-group change)	The Berg Balance Scale consists of 14 items testing the participant's ability to maintain positions of varying difficulty and to perform tasks such as transfer between positions, reach forward and alter stance positions. Each item is scored on a five-point ordinal scale ranging from 0 (cannot perform the task) to 4 (independence). Total scores can range from 0 to 56.	Pre- and post-intervention (6 and 12 months post stroke)
Secondary	Barthel-100 Index (between-group change)	The Barthel-100 Index is a clinical assessment of independence in activities of daily living (ADLs) through observation. The assessment has 10 items (feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, mobility, stairs) and participants may score 0-100 points. This measurement has been recommended as a part of a core outcome set.	Pre- and post-intervention (6 and 12 months post stroke)
Secondary	Global Rating of Change (between-group change)	Global Rating of Change is used to assess the participants' overall experience of change from pre- to post-intervention (T6-T12) and from post-intervention to follow-up (T12-T18). A seven-point likert scale is used. Participants will be asked to compare their current overall health to their health 6 months ago with answers ranging from "Much worse", "Little worse", "The same", "Little better", and "Much better.	12 and 18 months post stroke.
Secondary	International Physical Activity Questionnaire - Short Form (between-group change)	The International Physical Activity Questionnaire - Short Form is a patient-reported outcome measurement used to measure physical activity over the past week in four different intensity levels, including 1) vigorous activities, 2) moderate activities, 3) walking, and 4) sitting. Higher values equal higher levels of physical activity.	3, 6, 12, and 18 months post stroke.
Secondary	Fatigue Severity Scale 7 (between-group change)	The Fatigue Severity Scale 7 (FSS-7) is a one-dimensional 7-item patient reported outcome measurement commonly implemented in stroke trials. Each item is scored from one to seven with higher scores indicating increased fatigue. The FSS-7 was shown to be more valid than the 9-item version of the instrument (FSS-9), and therefore this version of the instrument is implemented.	3, 6, 12, and 18 months post stroke.
Secondary	EQ-5D-5L Quality of Life (between-group change)	The EQ-5D-5L (European Quality of Life - 5 Dimensions) is a validated survey for measuring health-related quality of life. It consists of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The outcome is reported on a scale of 1-5 where 1 is no problems and 5 is extreme problems. This measurement has been recommended as a part of a core outcome set.	3, 6, 12, and 18 months post stroke.
Secondary	Hand-grip strength (between-group change)	Hand-grip strength is a performance-based measurement assessed using a hand-held dynamometer. The outcome is in kilograms and used in the present study as an indicator for upper limb function.	Pre- and post-intervention (6 and 12 months post stroke)
Secondary	Gait speed (between-group change)	The 10-meter walking test is a performance-based measurement to evaluate gait speed. This test is recommended in two forms as a part of a core outcome set; 1) Can the person independently walk 10 metres (gait aids permitted) yes/no? and 2) gait speed on the 10-meter test if the person is able to independently walk 10 metres.	Pre- and post-intervention (6 and 12 months post stroke)