Rehabilitation after stroke often employs Robot and Allied Digital Technologies (RADTs), yet evidence on their effectiveness remains inconclusive due to study heterogeneity and limited sample sizes. This multicentre randomized controlled pragmatic trial aims at comprehensively and accurately assessing the effectiveness of rehabilitation mediated by RADTs after a stroke, compared to traditional rehabilitation, also considering economic sustainability.
The aim of this study is to evaluate, in a pragmatic trial on a large sample of patients who have experienced a stroke within the six months prior to enrollment, the effectiveness of a multimodal treatment using robotics and advanced technologies compared to traditional multimodal treatment, in the recovery of activities of daily living. Primary Objective: To demonstrate, in a population of subacute stroke patients, the non-inferiority of a rehabilitation treatment integrated with robotic and/or technological devices compared to traditional rehabilitative treatment in the recovery of activities of daily living. Secondary Objectives: * To demonstrate the superiority of rehabilitative treatment integrated with robotic and/or technological devices compared to traditional rehabilitation treatment in the recovery of activities of daily living, should non-inferiority be demonstrated; * To compare the improvements between two groups in all targeted domains (upper limb sensorimotor abilities; lower limb sensorimotor abilities and gait; balance; cognitive abilities), in accordance with the International Classification of Functioning, Disability, and Health (ICF); * To analyze the neurophysiological parameters and factors involved in neuroplasticity processes; * To compare the time pattern of manual dexterity and walking performance recovery in the two groups; * To assess the effects of the rehabilitation treatment in terms of daily life activities and quality of life through medium-term follow-up; * To evaluate the acceptability and usability of the rehabilitative treatment integrated with robotic and/or technological devices for the patient, their family, and the healthcare practitioner; * To create a predictive model capable of forecasting the effectiveness of robotic and technological treatment in subjects after a stroke, based on a detailed description of the patient at baseline (using demographic data and clinical picture at admission); * To assess the economic sustainability of the rehabilitative treatment integrated with robotic and/or technological devices for the patient, payer, and society, through the creation of a model for the assessment and prediction of cost-effectiveness, cost-utility, and, for the healthcare system, a Budget Impact Analysis, and related sensitivity analyses. The study employs a multicenter, multimodal, randomized, controlled, parallel-group (1:1) interventional design with blinded assessors, following a pragmatic approach. It will be conducted across multiple clinical centers involved in a national research initiative, encompassing both outpatient and inpatient settings. Randomization will be centralized and stratified by clinical center, latency, and clinical setting (inpatients or outpatients). The sample size (596 patients) was determined considering the following, with respect to the primary outcome (the change in the modified Barthel Index): (a) the non-inferiority of robotic treatment compared to traditional treatment; (b) a power of 80%; (c) a non-inferiority margin of 5 points; (d) a bilateral 95% confidence interval; (e) a standard deviation of the primary outcome of 20 points. Considering these parameters, a sample size of 506 patients (253 per group) is obtained. Additionally, considering a dropout rate of 15%, a total sample size of 596 patients is obtained. The same sample size is sufficient to also demonstrate the potential superiority of robotic treatment. In fact, considering a significance level of 5%, a power of 80%, a minimal clinically important difference of the scale of 9.25 points, a standard deviation of 20 points, and a dropout rate of 15%, a total of 178 patients are required for demonstrating superiority. The experimental group will receive rehabilitation using RADTs within a new organizational model, where two physical therapists supervise four to six patients. In the control group, patients will undergo individual traditional rehabilitation, maintaining a 1:1 patient-to-therapist ratio. In both groups, patients will undergo comprehensive rehabilitation treatment, targeting the following domains: a) upper limb sensorimotor abilities; b) lower limb sensorimotor abilities and gait; c) balance; d) cognitive abilities. The primary outcome is to demonstrate non-inferiority in activities of daily living as measured by the modified Barthel Index. Should non-inferiority be established, the study will then evaluate the potential superiority of RADTs in activities of daily living. All participating centers will follow a standardized operating procedure regarding treatment and outcome assessment to ensure consistency across all sites. Data will be systematically collected using the REDCap (Research Electronic Data Capture) platform.
Treatment will occur in a gym equipped with devices for all the domains, with two physiotherapists supervising groups of 4 to 6 patients, depending on their clinical severity. Patients will undergo a total of 25 sessions, each lasting 45 minutes, with the following frequency: * 5 times a week for 5 weeks, for inpatients; * 3 times a week for 8.3 weeks, for outpatients.
A physiotherapist-to-patient ratio of 1:1 is provided for the treatment in all participating centres. Patients will undergo a total of 25 sessions, each lasting 45 minutes, with the following frequency: * 5 times a week for 5 weeks, for inpatients; * 3 times a week for 8.3 weeks, for outpatients.
Fondazione Don Carlo Gnocchi, Centro Gala
Acerenza, Italy
RECRUITINGIRCCS Istituti Clinici Scientifici Maugeri
Bari, Italy
Change from baseline in the modified Barthel Index
The modified Barthel Index for Activities of Daily Living is a validated ordinal scale which measures a person's ability to complete activities of daily living (ADL). Scores range from 0 (total dependence) to 100 (total independence).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Fugl-Meyer Assessment for the upper extremities - motor function
The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The upper extremity motor function domain includes items assessing movement, coordination, and reflex action of the shoulder, elbow, forearm, wrist, and hand. It ranges from 0 (hemiplegia) to 66 (normal motor performance).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Fugl-Meyer Assessment for the upper extremities - sensory function
The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The upper extremity sensory function domain evaluates light touch on two surfaces of the arm, and position sense for upper limb joints. It ranges from 0 to 12 (normal sensory function).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Fugl-Meyer Assessment for the lower extremities - motor function
The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The lower extremity motor function domain includes items assessing movement, coordination, and reflex action of the hip, knee, and ankle. It ranges from 0 (hemiplegia) to 34 (normal motor performance).
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Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
596
IRCCS Ospedale Policlinico San Martino,
Genova, Italy
RECRUITINGFondazione Don Carlo Gnocchi, IRCCS Santa Maria Nascente
Milan, Italy
NOT_YET_RECRUITINGIRCCS Istituti Clinici Scientifici Maugeri
Milan, Italy
NOT_YET_RECRUITINGIRCCS Istituti Clinici Scientifici Maugeri
Montescano, Italy
RECRUITINGIRCCS Fondazione Mondino
Pavia, Italy
RECRUITINGIRCCS Istituti Clinici Scientifici Maugeri
Pavia, Italy
RECRUITINGFondazione Don Carlo Gnocchi, Centro Santa Maria della Provvidenza
Roma, Italy
RECRUITINGFondazione Don Carlo Gnocchi, Centro Santa Maria al Mare
Salerno, Italy
NOT_YET_RECRUITING...and 3 more locations
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Fugl-Meyer Assessment for the lower extremities - sensory function
The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. The lower extremity sensory function domain evaluates light touch on two surfaces of the leg, and position sense for lower limb joints. It ranges from 0 to 12 (normal sensory function).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Berg Balance Scale
The Berg Balance Scale (BBS) is used to objectively determine a patient's ability (or inability) to safely balance during a series of predetermined tasks. It is a 14-item scale designed to measure balance of the older adult in a clinical setting. It ranges from 0 to 56. A higher score indicates better balance.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Symbol Digit Modalities Test
The Symbol Digit Modalities Test evaluates information processing speed. It consists of a simple task of replacing symbols with numbers. Using a reference key, the patient has 90 seconds to match a sequence of symbols with the correspondent numbers as rapidly as possible. Both written or oral administration can be used. For each correct answer, a point is assigned. The higher the score, the faster the information processing speed.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Modified Ashworth Scale
The Modified Ashworth Scale (MAS) is a revised version of the original Ashworth Scale that measures spasticity in patients with lesions to the central nervous system. MAS is an assessment that is used to measure the increase in muscle tone. MAS assigns a grade of spasticity from a 0 to 4 ordinal scale. The grade is assigned by moving a joint/muscle through a high velocity quick stretch. The lower the score, the lower the spasticity. Upper and lower joints spasticity is assessed.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Motricity Index for upper extremities
The Motricity Index (MI) is an ordinal method of measuring limb strength. For upper extremity test, shoulder abduction, elbow flexion, pinch grip are considered. It ranges from 0 (worse) to 100 (normal strength).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Motricity Index for lower extremities
The Motricity Index (MI) is an ordinal method of measuring limb strength. For lower extremity test, hip flexion, knee extension, and ankle dorsiflexion are considered. It ranges from 0 (worse) to 100 (normal strength).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Trunk control test
The Trunk control test (TCT) measures four simple aspects of trunk movement. Total score range from 0 (minimum) to 100 (maximum, indicating better performance).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Numerical Rating Scale for Pain
The Numerical Rating Scale fo Pain (NRSP) is a subjective measure in which individuals rate their pain on an eleven-point numerical scale, from 0 (no pain) to 10 (worst pain imaginable).
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Neuropathic Pain 4 Questions
The Neuropathic Pain 4 Questions (DN4) is a validated clinician-administered screening tool for neuropathic pain. It ranges from 0 to 10; higher values means higher neuropathic pain probability.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Action Research Arm test
The Action Research Arm Test (ARAT) is a 19 item observational measure used to assess upper extremity performance (coordination, dexterity and functioning). The 19 items comprising the ARAT are scored using a 4 point ordinal scale. Scores on the ARAT may range from 0-57 points, with a maximum score of 57 points indicating better performance.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
2 Minute Walk Test
The 2 Minute Walk Test (2MWT) is a measure of self-paced walking ability and functional capacity. The person is encouraged to walk as fast as they can, safely, without assistance for two minutes and the distance is measured.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
5-level EQ-5D
The 5-level EQ-5D (EQ-5D-5L) is a validated tool to assess health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Brain Symmetry Index
The Brain Symmetry Index (BSI) is a quantitative electroencephalographic (qEEG) measure used to assess the degree of symmetry in brain activity between the two hemispheres. It is defined as the mean absolute difference in spectral power of the EEG signals from homologous channels pairs on the left and right hemispheres, in the frequency range from 1 to 25 Hz. A higher BSI value indicates greater asymmetry, which is often associated with poorer clinical outcomes in stroke patients.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Delta/Alpha Ratio
The Delta/Alpha Ratio (DAR) is a quantitative electroencephalographic (qEEG) measure used to assess the balance between slow-wave (delta) and fast-wave (alpha) brain activity. It is calculated by dividing the power of delta waves (0.5-4 Hz) by the power of alpha waves (8-12 Hz). The DAR is particularly useful in evaluating brain function in stroke patients, as an increased DAR is often associated with greater brain dysfunction and poorer clinical outcomes.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Change in serum concentration of Glial Fibrillary Acidic Protein (GFAP)
Serum GFAP Concentration will be evaluated by "Ella" automated Immunoassay System method.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Serum concentration of Neurofilament light (NfL)
Serum NfL Concentration will be evaluated by "Ella" automated Immunoassay System method.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
Serum concentration of Brain Derived Neurotrophic Factor (BDNF)
Serum BDNF Concentration will be evaluated by "Ella" automated Immunoassay System method.
Time frame: baseline; within 24 hours from the 25th rehabilitation session
10 Meter Walk Test
The 10 Meter Walk Test is a performance measure used to assess walking or gait speed in meters per second over a distance of 10 meters
Time frame: baseline; within 24 hours from: the 5th rehabilitation session; the 10th rehabilitation session; the 15th rehabilitation session; the 20th rehabilitation session; the 25th rehabilitation session
Box and block test
The Box and Block Test (BBT) measures unilateral gross manual dexterity. It is a quick, simple and inexpensive test. The individual is instructed to move as many blocks as possible, one at a time, from one compartment to the other of a test box with 150 blocks and a partition in the middle. The number of blocks transferred in 60 seconds is recorded. Both the affected and the not affected side are measured.
Time frame: baseline; within 24 hours from: the 5th rehabilitation session; the 10th rehabilitation session; the 15th rehabilitation session; the 20th rehabilitation session; the 25th rehabilitation session
modified Barthel Index (follow-up)
The Barthel Index for Activities of Daily Living is a validated ordinal scale which measures a person's ability to complete activities of daily living (ADL). Scores range from 0 (total dependence) to 100 (total independence).
Time frame: 1 month after the end of the treatment; 2 months after the end of the treatment; 3 months after the end of the treatment; 4 months after the end of the treatment; 5 months after the end of the treatment; 6 months after the end of the treatment;
EQ-5D-5L (follow-up)
The 5-level EQ-5D version (EQ-5D-5L) is a validated tool to assess health-related quality of life. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Index scores range from -0.59 to 1; 1 is the best possible health state. Negative values represent health states perceived as worse than dead, which is equal to 0.
Time frame: 1 month after the end of the treatment; 2 months after the end of the treatment; 3 months after the end of the treatment; 4 months after the end of the treatment; 5 months after the end of the treatment; 6 months after the end of the treatment;