Rehabilitation With and Without Robot and Allied Digital Technologies in Stroke Patients
- Conditions
- Stroke
- Interventions
- Other: traditional rehabilitationOther: robotic rehabilitation
- Registration Number
- NCT06547827
- Lead Sponsor
- Fondazione Don Carlo Gnocchi Onlus
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 596
- First-ever diagnosis of ischemic or haemorrhagic stroke confirmed by Computed Tomography or Magnetic Resonance Imaging;
- Age 18 years and over;
- Time since the event equal to or less than 6 months;
- Mild to severe impairment of the upper limb (motor section of the Fugl-Meyer Assessment of Upper Extremity ≤ 58) and/or mild to severe impairment of the lower limb (score on the Functional Ambulation Categories scale ≤ 4) and/or mild to severe impairment of balance (Berg Balance Scale ≤ 45);
- Clinical stability allowing transfer to the gym and execution of the planned treatments.
- Clinical instability;
- Behavioral/cognitive disorders preventing adequate patient compliance with both traditional and robotic rehabilitation treatment (severe cognitive deficit, Montreal Cognitive Assessment <10);
- Rigidity or hypertonia (Modified Ashworth Scale > 3) in the plegic/paretic limb;
- Serious uncorrectable visual impairments preventing the patient from performing treatment with technological and/or robotic devices;
- Pregnant women;
- Refusal to sign the informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Traditional Treatment traditional rehabilitation In the control group, subjects will undergo a standard traditional rehabilitation program without the use of RADTs, focusing on the following domains:a) upper limb sensorimotor abilities; b) lower limb sensorimotor abilities and gait; c) balance; and d) cognitive abilities, using traditional methods of physiotherapy and cognitive rehabilitation. Integrated Treatment with Robotic & Technological Devices (RADTs) robotic rehabilitation This intervention employs various RADTs to target the following domains: a) upper limb sensorimotor abilities; b) lower limb sensorimotor abilities and gait; c) balance; and d) cognitive abilities. For upper limb sensorimotor function, we will use planar end-effector robots, exoskeletons, or electromechanical systems for shoulder, elbow, and wrist rehabilitation; end-effector robots or exoskeletons for hand rehabilitation; and sensor-based devices for comprehensive upper limb treatment. For lower limb sensorimotor function, we will utilize end-effector robots or exoskeletons and treadmills with body-weight support systems. Balance training will involve stabilometric platforms and sensor-based systems. Cognitive functions will be addressed using digital systems, sensor-based devices, and virtual reality programs. All devices must have a CE mark for medical devices and be used according to the manufacturer's specifications.
- Primary Outcome Measures
Name Time Method Change from baseline in the modified Barthel Index baseline; within 24 hours from the 25th rehabilitation session 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).
- Secondary Outcome Measures
Name Time Method 2 Minute Walk Test baseline; within 24 hours from the 25th rehabilitation session 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.
Action Research Arm test baseline; within 24 hours from the 25th rehabilitation session 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.
Fugl-Meyer Assessment for the upper extremities - sensory function baseline; within 24 hours from the 25th rehabilitation session 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).
Neuropathic Pain 4 Questions baseline; within 24 hours from the 25th rehabilitation session 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.
Fugl-Meyer Assessment for the lower extremities - motor function baseline; within 24 hours from the 25th rehabilitation session 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).
Motricity Index for upper extremities baseline; within 24 hours from the 25th rehabilitation session 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).
Fugl-Meyer Assessment for the upper extremities - motor function baseline; within 24 hours from the 25th rehabilitation session 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).
Berg Balance Scale baseline; within 24 hours from the 25th rehabilitation session 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.
Modified Ashworth Scale baseline; within 24 hours from the 25th rehabilitation session 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.
Numerical Rating Scale for Pain baseline; within 24 hours from the 25th rehabilitation session 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).
Change in serum concentration of Glial Fibrillary Acidic Protein (GFAP) baseline; within 24 hours from the 25th rehabilitation session Serum GFAP Concentration will be evaluated by "Ella" automated Immunoassay System method.
Serum concentration of Brain Derived Neurotrophic Factor (BDNF) baseline; within 24 hours from the 25th rehabilitation session Serum BDNF Concentration will be evaluated by "Ella" automated Immunoassay System method.
modified Barthel Index (follow-up) 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; 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).
Fugl-Meyer Assessment for the lower extremities - sensory function baseline; within 24 hours from the 25th rehabilitation session 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).
Symbol Digit Modalities Test baseline; within 24 hours from the 25th rehabilitation session 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.
Motricity Index for lower extremities baseline; within 24 hours from the 25th rehabilitation session 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).
Trunk control test baseline; within 24 hours from the 25th rehabilitation session The Trunk control test (TCT) measures four simple aspects of trunk movement. Total score range from 0 (minimum) to 100 (maximum, indicating better performance).
Brain Symmetry Index baseline; within 24 hours from the 25th rehabilitation session 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.
10 Meter Walk Test 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 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
5-level EQ-5D baseline; within 24 hours from the 25th rehabilitation session 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.
Delta/Alpha Ratio baseline; within 24 hours from the 25th rehabilitation session 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.
Serum concentration of Neurofilament light (NfL) baseline; within 24 hours from the 25th rehabilitation session Serum NfL Concentration will be evaluated by "Ella" automated Immunoassay System method.
Box and block test 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 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.
EQ-5D-5L (follow-up) 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; 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.
Trial Locations
- Locations (9)
Fondazione Don Carlo Gnocchi, Centro Gala
🇮🇹Acerenza, Italy
IRCCS Istituti Clinici Scientifici Maugeri
🇮🇹Telese Terme, Italy
IRCCS Ospedale Policlinico San Martino,
🇮🇹Genova, Italy
Fondazione Don Carlo Gnocchi, IRCCS Santa Maria Nascente
🇮🇹Milan, Italy
IRCCS Fondazione Mondino
🇮🇹Pavia, Italy
Fondazione Don Carlo Gnocchi, Centro Santa Maria della Provvidenza
🇮🇹Roma, Italy
Fondazione Don Carlo Gnocchi, Centro Santa Maria al Mare
🇮🇹Salerno, Italy
Fondazione Don Carlo Gnocchi, Polo Specialistico Riabilitativo
🇮🇹Sant'Angelo Dei Lombardi, Italy
Fondazione Don Carlo Gnocchi, Polo specialistico riabilitativo
🇮🇹Tricarico, Italy