Telerehabilitation in Progressive Multiple Sclerosis
NCT Number: NCT06485115
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Progressive Multiple Sclerosis
Interventions: DEVICE: Digital Telerehabilitation (Euleria Home)|OTHER: Conventional therapy
Sponsor: Universita di Verona
Collaborators: Università degli Studi di Ferrara
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 78
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-06-30
Completion Date: 2026-06-30
Locations: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, 37131, Italy

Summary:
Multiple sclerosis (MS) is a highly disabling chronic, inflammatory, demyelinating disease of the Central Nervous System (CNS). Significant progress has been made during the past three decades in managing the relapsing-remitting phase of Multiple Sclerosis (RRMS). However, once patients have entered the progressive stage of MS (secondary progressive, SPMS), therapeutic options are limited to symptomatic treatments and rehabilitation. In addition, 10-20% of patients experience unremitting disease progression (primary progressive MS, or PPMS). The limited research focusing on Progressive MS (PMS) and the lack of ecological validity highlight the need for a bolder approach that combines more than one intervention intending to produce synergistic effects. The primary aim is to test the effectiveness of combining a home-based Digital Telerehabilitation program with in-hospital rehabilitation on mobility against in-hospital rehabilitation alone.

Primary Outcome Measures: Change in the Timed Up and Go test, The patient mobility will be measured by the Timed Up and Go (TUG) test (Euleria Lab, Rovereto - TN, Italy). We will give patients verbal instructions to stand up from a chair, walk 3 meters, cross a line marked on the floor, turn around, walk back, and sit down., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)
Secondary Outcome Measures: Change in the Multiple Sclerosis Functional Composite (MSFC), Multiple Sclerosis Functional Composite (MSFC) is a multidimensional, three-component performance scale to assess the degree of impairment in MS patients: gait, upper extremity function, and cognition. Since the units of three variables measured by three tests are different (Timed 25-foot Walk Test (T25FW) and 9-Hole Peg Test (9HPT) and number of correct answers in 3-second version of the Paced Auditory Serial Addition Test (PASAT-3)), raw scores should be converted to a common metric, namely z-scores. The overall composite score (MSFC score) is calculated by adding the z-scores for each test. Component scores are entered into a formula with scores from the reference population in order to derive the means and standard deviations required to determine Z-scores. A score of +1 indicates that, on average, an individual scored 1 SD better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Mental workload through Electroencephalography (EEG) during Multiple Sclerosis Functional Composite Score, During the Multiple Sclerosis Functional Composite (MSFC) administration, the participant's brain activity will be recorded using electroencephalography (EEG) to assess the participant's mental workload and vigilance state during the task., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Vigilance state through Electroencephalography (EEG) during Multiple Sclerosis Functional Composite Score, During the Multiple Sclerosis Functional Composite (MSFC) administration, the participant's brain activity will be recorded using electroencephalography (EEG) to assess the participant's vigilance state during the task., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Surface electromyography (EMG) during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC)., The muscular activity of the upper limb will be recorded using surface electromyography (EMG) system during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC)., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Inertial Measurement Unit (IMU) system during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC)., The kinematics of the upper limb will be recorded using Inertial Measurement Unit (IMU) system during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC)., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Fatigue Severity Scale (FSS), The Fatigue Severity Scale (FSS) is a self-administered questionnaire with 9 items (questions) investigating the severity of fatigue in different situations. The items are scored on a 7 point scale (1= strongly disagree and 7= strongly agree). The minimum score is 9 and maximum score possible is 63. Higher score indicate greater fatigue severity., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Activities-specific balance confidence (ABC), The Activities-specific balance confidence (ABC) Scale is a self-report measure of balance confidence in performing various activities without losing balance or experiencing a sense of unsteadiness. It is a 16-item self-report measure in which patients rate their balance confidence for performing activities. Items are rated on a rating scale that ranges from 0 - 100. Score of zero represents no confidence, a score of 100 represents complete confidence. Overall score is calculated by adding item scores and then dividing by the total number of items., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Manual Ability Measure-36 (MAM-36), The Manual Ability Measure-36 (MAM-36) is designed as an outcome instrument to assess hand function based on the patient's responses to functional questions. Patient rates functional abilities based on his or her perception of the difficulty or ease in completing one or two-handed daily tasks. Item level scores are as follows: 1=cannot do, 2=very hard, 3=a little hard and 4=easy, 0=not applicable/almost never do. The total score ranging from 0 to 144; higher scores indicate better-perceived manual ability., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|The number of falls in the previous month, Number of falls in the previous month, Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Timed Up and Go (TUG) test - Cognitive, In the Timed Up and Go (TUG) test - Cognitive, individuals will be asked to complete the test while counting backward by threes from a randomly selected number between 20 and 100, Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Electroencephalography (EEG) during the Timed Up and Go (TUG) test - Cognitive, During the Timed Up and Go (TUG) test - Cognitive, the participant's brain activity will be recorded using electroencephalography (EEG) to assess the participant's mental workload and vigilance state during the task, Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Timed Up and Go (TUG) test - Manual, In the Timed Up and Go (TUG) test - Manual, individuals will be asked to complete the test holding a cup filled with water., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Electroencephalography (EEG) during the Timed Up and Go (TUG) test - Manual, During the Timed Up and Go (TUG) test - Manual, the participant's brain activity will be recorded using electroencephalography (EEG) to assess the participant's mental workload and vigilance state during the task, Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the gait speed (cm/s), Gait analysis will be used to collect gait speed (cm/s), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the cadence (step/min), Gait analysis will be used to collect cadence (step/min), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the stride length (cm), Gait analysis will be used to collect stride length (cm), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the length of the centre of pressure (CoP), Stabilometric platform will be used to evaluated the length of the centre of pressure (CoP), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the trajectory (mm), Stabilometric platform will be used to evaluated the trajectory (mm), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the sway area (mm2), Stabilometric platform will be used to evaluated the sway area (mm2), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Brief Pain Inventory (BPI), The Brief Pain Inventory (BPI) is a self-administered questionnaire divided into intensity (range: 0-40; higher = worse) and interference (range: 0-70; higher = worse), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Hospital Anxiety and Depression Scale, The Hospital Anxiety and Depression Scale (HADS) is a brief self-report questionnaire composed of 14 items (7 items each for anxiety and depression), with a score ranging between 0 and 21 for the anxiety and depression subscales. Scores between 8 and 10 indicate a moderate presence of symptoms, whereas a score greater than 11 indicates a significant number of symptoms that likely correspond with a clinical diagnosis., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Hospital Anxiety and Depression Scale - Anxiety (HADS-A), The Hospital Anxiety and Depression Scale - Anxiety (HADS-A, 7 items) subscale scores will be calculated, possibly ranging from 0 (no symptoms) to 21 (most severe symptoms), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Hospital Anxiety and Depression Scale - Depression (HADS-D), The Hospital Anxiety and Depression Scale - Depression (HADS-D, 7 items) subscale scores will be calculated, possibly ranging from 0 (no symptoms) to 21 (most severe symptoms), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Modified Asworth Scale, The Modified Ashworth Scale is a 6-points muscle tone assessment scale used to assess the resistance experienced during passive range of motion. Scores range from 0 to 4, where lower scores represent normal muscle tone and higher scores represent spasticity., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Modified Tardieu Scale, The Modified Tardieu Scale si a clinical measure of muscle spasticity in patients with neurological conditions. The Modified Tardieu Scale comprises four elements, including R1, R2, R2-R1 and X score. R1 represents an angle of catch, where a sudden increase of muscle resistance is felt during a fast passive stretch. R2 is an angle indicating the tested muscle length at a slow passive range of motion. R2-R1 was introduced to differentiate spasticity from contracture.15 Contracture is indicated if the value of R2-R1 is small, while a large value indicates spasticity. The X score describes types of muscle resistance when passive stretches are applied during the assessment (grade 0-5). Quality of Muscle Reaction (scored 0-5); 0 is no resistance to passive ROM to 5 indicating joint is immobile., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the the Multiple Sclerosis Quality Of Life-54 (MSQOL-54), The MSQOL-54 is a multidimensional health-related quality of life measure that combines both generic and MS-specific items into a single instrument. This 54-item instrument generates 12 subscales along with two summary scores, and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The summary scores are the physical health composite summary and the mental health composite summary. The single item measures are satisfaction with sexual function and change in health. There is no single overall score for the MSQOL-54. Two summary scores - physical health and mental health - can be derived from a weighted combination of scale scores., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|The EuroQol five domains (EQ-5D), The EuroQol five-dimensions (EQ5D) is a versatile quality of life (QOL) instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analog scale. It can be used to calculate quality-adjusted life years. The scale ranges from 100 ('the best imaginable health state' or 'the best health state you can imagine') to 0 ('the worst imaginable health state' or 'the worst health you can imagine')., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|The volumes of health services, The volumes of health services will be collected at baseline encompassing the resources use 6 months prior the start of the study and 24 weeks after the in-hospital treatment (T3) estimating the resource use during the entire trial duration, Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)|The Multiple Sclerosis Health Resource Utilization Survey (MS-HRS), Direct healthcare costs will be assessed using the Multiple Sclerosis Health Resource Utilization Survey (MS-HRS). The Multiple Sclerosis Health Resource Utilization Survey (MS-HRS) is a multilingual, reliable, valid and easy to administer questionnaire providing a holistic cross-sectional and longitudinal assessment of resource utilization in people with multiple sclerosis., Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)|The TheiTA Productivity Cost Questionnaire, Indirect costs will be measured using validated log as the TheiTA Productivity Cost Questionnaire for productivity loss, Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)|Change in the Clinical Global Impression (CGI), Self-rated perception of change will be assessed with the 7-point Clinical Global Impression (CGI) scale with scores from 1 (very much improved) to 7 (very much worse), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Changes in effective brain connectivity through Electroencephalography (EEG), Only patients eligible for EEG will be evaluated to detect changes in effective brain connectivity through EEG during a motor observation, execution, and motor imagery task., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Brief Illness Perception Questionnaire (B-IPQ), The Brief Illness Perception Questionnaire (B-IPQ) consists of eight items on an individual's cognitive and emotional representation of one's health conditions.To score the B-IPQ questionnaire, each item is rated on a 0-10 scale, with higher scores indicating a more threatening perception of the illness. The total score is calculated by summing the scores of all eight items, with a possible range of 0-80. Higher scores indicate worse illness perception., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Multidimensional Psychological Flexibility Inventory (MPFI), The Multidimensional Psychological Flexibility Inventory (MPFI), a 60-item scale that measures the 6 dimensions of psychological flexibility and the 6 dimensions of inflexibility posited by the Hexaflex model. To score the Multidimensional Psychological Flexibility Inventory subscales, are assigned responses point values from 1 to 6 and then average the responses across the items of each scale so that higher scores reflect higher levels of the dimension being assessed by each set of items. The averages of the 6 flexibility subscales can be averaged to create a composite representing global flexibility. Similarly, the averages of the 6 inflexibility subscales can be averaged to create a global inflexibility composite., Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Change in the Self-Efficacy for Multiple Sclerosis Scale (SEMS), The Self-Efficacy for Multiple Sclerosis Scale (SEMS) assesses self-efficacy related to the management of MS. It comprises 15 items starting from the root statement "I am confident that I can..." and is rated on a 5-point Likert scale from 0 (Not at all confident) to 4 (Very confident), Before treatment (T0), after 4 weeks of in-hospital rehabilitation (T1), at the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2), and 24 weeks after the in-hospital treatment (T3)|Tele-healthcare Satisfaction Questionnaire-Wearable Technology, Tele-healthcare Satisfaction Questionnaire-Wearable Technology consists of 6 areas (benefit, usability, self-concept, privacy and loss of control, quality of life, and wearing comfort) that evaluate the satisfaction of the subject with the wearable part of a system. Each area includes 5 statements rated by the user on a 5-point Likert scale between 0 (strongly disagree with the statement) and 4 (strongly agree with the statement), At the end of the 12 weeks of telerehabilitation|Patients' In-home Digital Telerehabilitation training experience questionnaire, One questionnaire used by the research group to evaluate patients' In-home Digital Telerehabilitation training experience with the Digital Telerehabilitation program "EG treatment experience". The questionnaire consists of 9 questions scored on a 10-point scale (1=not at all; 10=very much) and 17 open-ended questions to investigate pleasantness, usefulness, acceptability, safety, satisfaction, and future development., At the end of the 12 weeks of telerehabilitation|Activity levels through Technology-based Objective Measures (TOMS), Wearable sensors (Axivity AX3) will be used to collect the activity levels., After 4 weeks of in-hospital rehabilitation (T1), At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)|Number of steps through Technology-based Objective Measures (TOMS), Wearable sensors (Axivity AX3) will be used to collect the number of steps., After 4 weeks of in-hospital rehabilitation (T1), At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)|Distance traveled through Technology-based Objective Measures (TOMS), Wearable sensors (Axivity AX3) will be used to collect the distance traveled., After 4 weeks of in-hospital rehabilitation (T1), At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)|Risk of fall assessment, An inertial sensor will be used to detect near falls during balance training and i twill be placed on the forehead with an elastic band., During the 4 weeks in-hospital rehabilitation (3 days/week for 4 week - total of 10 sessions)|Adverse Events, Safety in terms of reported adverse events during the treatment (falls or event near falling) will be collected, At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)|Number of patients who accept/refuse the treatment, Measures of feasibility in terms of the recruitment rate before the end of treatment will be collected., At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)|Number of dropouts, Measures of feasibility in terms of the number of dropouts before the end of treatment will be collected, At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)