Telerehabilitation in Progressive Multiple Sclerosis

The Effectiveness of Combining a Home-based Digital Motor Telerehabilitation Program With Conventional Therapy in Progressive Multiple Sclerosis: a Multicentre, Randomized Controlled Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Device: Digital Telerehabilitation (Euleria Home); Other: Conventional therapy

Detailed Description

The literature emphasizes a striking dearth of studies devoted solely to people with SPMS or PPMS and the lack of ecological validity in assessing the results. This suggests that an additional effort is required, a bolder approach that combines more than one intervention intending to produce synergistic effects, an improvement in one area boosting the putative benefits of therapy in another, the overall outcome exceeding the sum of the individual treatments.

The primary aim will be to test the effectiveness of combining a home-based digital motor telerehabilitation program (experimental intervention) with in-hospital rehabilitation on mobility (primary outcome) against in-hospital rehabilitation without any additional therapy except for general instructions for self-management as usual care (conventional treatment) in patients with SPMS or PPMS.

The secondary aims will be to explore the effects on measures of motor and cognitive function; the patients reported outcomes on balance and upper extremity function, fatigue, pain, anxiety, and depressive symptoms; the self-perception of clinical change; and Health-Related Quality of Life. Furthermore, the investigators will explore the patient's perspective and experience with Digital Telerehabilitation post-treatment using quantitative-qualitative methods (EG intervention). An economic evaluation of the introduction of the digital telemedicine program will be carried out within the health technology assessment (HTA) framework, considering the perspective of the healthcare system and society as a whole.

This single-blind RCT with 2-parallel arms will compare the effects between the experimental group (EG) and control group (CG). After the screening, an administrator external to research groups (the principal investigator) will generate a block randomization list at each Unit to prevent selection bias using an automated randomization system (www.randomization.com) (allocation ratio 1:1) to assign eligible patients to either the EG or the CG. Patients will be stratified according to the EDSS (≥ 6 and < 6). Group allocation will be kept concealed. All patients will receive an individualized ten sessions of an in-hospital rehabilitation program (1 hour/day, 3 days/week) by a qualified physiotherapist at each participating unit. Then, the EG will follow a 12-week individualized Digital Telerehabilitation program (1 hour/day, 3 days/week, EG) while the CG will not receive any additional therapy except for general instructions for self-management according to the allocation group. All the patients will undergo four clinical evaluations: before (T0) and after (T1) the in-hospital rehabilitation program, 12 weeks (T2), and 24 weeks (follow-up, T3) after it. One researcher assistant with experience in assessing primary and secondary outcomes blinded to group assignment will evaluate study participants at all time points in each Unit.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marialuisa Gandolfi, PhD; Phone Number: +390458124943; Email: marialuisa.gandolfi@univr.it
• Study Contact Backup: Name: Marialuisa Gandolfi; Phone Number: 3491656108; Email: marialuisa.gandolfi@univr.it

Study Locations

• Italy
  • Verona, Italy, 37131
    • Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-75;
• Diagnosis of MS (primary or secondary progressive);
• Mild to moderate balance impairments with increased fall risk, defined as TUG > 8.4s;
• A disability rate, as calculated using the Kurtzke Expanded Disability Status Scale (EDSS) lower than 7;
• Acceptable level of digital skills;
• The presence of the caregiver.

Exclusion Criteria:

• Other conditions that may affect motor function;
• Impaired cognitive functioning (Mini-Mental Status Examination <24/30);
• Severe visual deficits (daltonism and visual acuity deficit);
• Unable or refused to attend the rehabilitation treatment.

Patients who fulfill the following specified inclusion criteria will also undergo an EEG evaluation. However, ineligibility for this examination does not exclude them from participating in the rehabilitation study.

The inclusion criteria for the EEG protocol will include:

• The absence of metallic implants in the brain;
• No history of brain surgery;
• No use of medications that alter cortical excitability or are presumed to affect brain plasticity;
• Right-handed dominance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Home-based Digital motor Telerehabilitation added to conventional therapy; All patients will receive an individualized ten sessions of an in-hospital rehabilitation program (1 hour/day, 3 days/week) by a qualified physiotherapist at each participating unit. Then, the EG will follow a 12-week individualized Digital Telerehabilitation program (1 hour/day, 3 days/week, EG).	Device: Digital Telerehabilitation (Euleria Home); After the in-hospital rehabilitation treatment (1 h/day, 3 days/week), the EG patients will perform the Digital Telerehabilitation program at home. The three weekly sessions will be asynchronous (with the caregiver's supervision if necessary). At each Unit, the physiotherapist will develop the training sessions on the Home- based Digital Telerehabilitation program and monitor the training execution provided by the digital device to adapt the rehabilitation treatment to the patients' improvements/difficulties. The Digital Telerehabilitation device (Euleria Home, Euleria Health) will consist of one wearable sensor and an app on a tablet that guides the patient through the customized exercise-therapy path configured by the professional. The sensor is worn on different body segments to monitor movements and provides real-time feedback on angles, balance, and repetitions.; Other: Conventional therapy; After the in-hospital rehabilitation treatment (1 h/day, 3 days/week), the CG patients will be advised to perform the Self-management activities learned during the in-hospital rehabilitation training without home-based Digital Telerehabilitation devices.
Other: Conventional therapy alone; All patients will receive an individualized ten sessions of an in-hospital rehabilitation program (1 hour/day, 3 days/week) by a qualified physiotherapist at each participating unit. Then, the CG will not receive any additional therapy except for general instructions for self- management according to the allocation group.	Other: Conventional therapy; After the in-hospital rehabilitation treatment (1 h/day, 3 days/week), the CG patients will be advised to perform the Self-management activities learned during the in-hospital rehabilitation training without home-based Digital Telerehabilitation devices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Universita di Verona
• Collaborators: Università degli Studi di Ferrara
• Investigators: Principal Investigator: Marialuisa Gandolfi, Universita di Verona

Publications and helpful links

General Publications

• Buchholz I, Janssen MF, Kohlmann T, Feng YS. A Systematic Review of Studies Comparing the Measurement Properties of the Three-Level and Five-Level Versions of the EQ-5D. Pharmacoeconomics. 2018 Jun;36(6):645-661. doi: 10.1007/s40273-018-0642-5.
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• Broadbent E, Petrie KJ, Main J, Weinman J. The brief illness perception questionnaire. J Psychosom Res. 2006 Jun;60(6):631-7. doi: 10.1016/j.jpsychores.2005.10.020.
• Powell LE, Myers AM. The Activities-specific Balance Confidence (ABC) Scale. J Gerontol A Biol Sci Med Sci. 1995 Jan;50A(1):M28-34. doi: 10.1093/gerona/50a.1.m28.
• Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996 Apr;46(4):907-11. doi: 10.1212/wnl.46.4.907.
• Gandolfi M, Geroin C, Picelli A, Munari D, Waldner A, Tamburin S, Marchioretto F, Smania N. Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial. Front Hum Neurosci. 2014 May 22;8:318. doi: 10.3389/fnhum.2014.00318. eCollection 2014.
• Shumway-Cook A, Brauer S, Woollacott M. Predicting the probability for falls in community-dwelling older adults using the Timed Up & Go Test. Phys Ther. 2000 Sep;80(9):896-903.
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Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Balance; Cognitive Function; Wearables; Dual Task; Digital Telemedicine
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
• Other Study ID Numbers: 2023/R-Multi/010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No