Clinical trial NCT06547827: Rehabilitation With and Without Robot and Allied Digital Technologies in Stroke Patients
Official title: Rehabilitation With and Without Robot and Allied Digital Technologies (RADTs) in Stroke Patients: a Pragmatic Multicenter Randomised Controlled Trial on the Effectiveness, Acceptability, Usability, and Economic-organizational Sustainability of RADTs From Subacute to Chronic Phase
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Keywords: rehabilitation
robotics
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
Collaborators: name: Istituti Clinici Scientifici Maugeri SpA
name: IRCCS National Neurological Institute "C. Mondino" Foundation
name: Ospedale Policlinico San Martino
name: Università di Pavia
name: Scuola Superiore Sant'Anna di Pisa
First posted: 2024-08-09
Enrollment: 596
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change from baseline in the modified Barthel Index
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
Secondary outcomes:
measure: Fugl-Meyer Assessment for the upper extremities - motor function
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Fugl-Meyer Assessment for the upper extremities - sensory function
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Fugl-Meyer Assessment for the lower extremities - motor function
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Fugl-Meyer Assessment for the lower extremities - sensory function
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Berg Balance Scale
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Symbol Digit Modalities Test
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Modified Ashworth Scale
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Motricity Index for upper extremities
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Motricity Index for lower extremities
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Trunk control test
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Numerical Rating Scale for Pain
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Neuropathic Pain 4 Questions
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Action Research Arm test
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: 2 Minute Walk Test
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: 5-level EQ-5D
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Brain Symmetry Index
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Delta/Alpha Ratio
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Change in serum concentration of Glial Fibrillary Acidic Protein (GFAP)
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Serum concentration of Neurofilament light (NfL)
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Serum concentration of Brain Derived Neurotrophic Factor (BDNF)
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: 10 Meter Walk Test
timeFrame: 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
measure: Box and block test
timeFrame: 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
measure: modified Barthel Index (follow-up)
timeFrame: 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;
measure: EQ-5D-5L (follow-up)
timeFrame: 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;
Other outcomes:
measure: premorbid Modified Rankin Scale
timeFrame: At baseline
measure: Life Time Physical Activity Questionnaire
timeFrame: At baseline
measure: Cognitive Reserve Index
timeFrame: At baseline
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: At baseline
measure: Cumulative Illness Rating Scale - severity index
timeFrame: At baseline
measure: Cumulative Illness Rating Scale - comorbidity index
timeFrame: At baseline
measure: Thumb Localizing Test
timeFrame: At baseline
measure: Semmes Weinstein filament test
timeFrame: At baseline
measure: Fatigue Severity Scale
timeFrame: At baseline
measure: Blaylock Risk Assessment Screening Score
timeFrame: At baseline
measure: Montreal Cognitive Scale
timeFrame: At baseline
measure: Intrinsic Motivation Inventory
timeFrame: within 24 hours from the 5th rehabilitation session
measure: Hospital Anxiety and Depression Scale
timeFrame: At baseline
measure: Beck Depression Inventory
timeFrame: At baseline
measure: Mini Nutritional Assessment Short-Form
timeFrame: At baseline
measure: SARC-F
timeFrame: At baseline
measure: Functional Oral Intake Scale
timeFrame: At baseline
measure: Handgrip test
timeFrame: At baseline
measure: Number of patients with the Brain Derived Neurotrophic Factor (BDNF) genetic polymorphism rs6265 (Val66Met) classified by genotype: homozygous GG (Valine/Valine), heterozygous GA (Valine/Methionine), or homozygous AA (Methionine/Methionine).
timeFrame: At baseline
measure: 5-level EQ-5D
timeFrame: baseline; within 24 hours from the 15th rehabilitation session; within 24 hours from the 25th rehabilitation session
measure: Computer skills questionnaire
timeFrame: At baseline
measure: Technology Acceptance Model
timeFrame: within 24 hours from the 5th rehabilitation session; within 24 hours from the 15th rehabilitation session; within 24 hours from the 25th rehabilitation session
measure: Questionnaire for satisfaction
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Questionnaire for perception of problems and solution complexity
timeFrame: baseline; within 24 hours from the 25th rehabilitation session
measure: Questionnaire for costs
timeFrame: baseline; within 24 hours from the 15th rehabilitation session; within 24 hours from the 25th rehabilitation session
measure: Incremental cost-utility ratio
timeFrame: During the study,an average of 24 months
measure: Incremental cost-effectiveness ratio
timeFrame: During the study, an average of 24 months
measure: Financial impact (differences in direct health costs)
timeFrame: During the study, an average of 24 months
Locations:
city: Acerenza
country: Italy
facility: Fondazione Don Carlo Gnocchi, Centro Gala
city: Bari
country: Italy
facility: IRCCS Istituti Clinici Scientifici Maugeri
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino,
city: Milan
country: Italy
facility: Fondazione Don Carlo Gnocchi, IRCCS Santa Maria Nascente
city: Milan
country: Italy
facility: IRCCS Istituti Clinici Scientifici Maugeri
city: Montescano
country: Italy
facility: IRCCS Istituti Clinici Scientifici Maugeri
city: Pavia
country: Italy
facility: IRCCS Fondazione Mondino
city: Pavia
country: Italy
facility: IRCCS Istituti Clinici Scientifici Maugeri
city: Roma
country: Italy
facility: Fondazione Don Carlo Gnocchi, Centro Santa Maria della Provvidenza
city: Salerno
country: Italy
facility: Fondazione Don Carlo Gnocchi, Centro Santa Maria al Mare
city: Sant'Angelo Dei Lombardi
country: Italy
facility: Fondazione Don Carlo Gnocchi, Polo Specialistico Riabilitativo
city: Telese Terme
country: Italy
facility: IRCCS Istituti Clinici Scientifici Maugeri
city: Tricarico
country: Italy
facility: Fondazione Don Carlo Gnocchi, Polo specialistico riabilitativo
Study officials:
affiliation: IRCCS Fondazione Don Carlo Gnocchi
name: Irene G Aprile
role: STUDY_DIRECTOR
affiliation: IRCCS Fondazione Don Carlo Gnocchi
name: Irene G Aprile
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Istituti Clinici Scientifici Maugeri
name: Christian Lunetta
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Fondazione Mondino
name: Roberto De Icco
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Ospedale Policlinico San Martino
name: Carlo Trompetto
role: PRINCIPAL_INVESTIGATOR
affiliation: Università di Pavia
name: Silvana Quaglini
role: PRINCIPAL_INVESTIGATOR
affiliation: Scuola Superiore Sant'Anna di Pisa
name: Giuseppe Turchetti
role: PRINCIPAL_INVESTIGATOR
References: