Clinical trial NCT06485115: Telerehabilitation in Progressive Multiple Sclerosis
Official title: The Effectiveness of Combining a Home-based Digital Motor Telerehabilitation Program With Conventional Therapy in Progressive Multiple Sclerosis: a Multicentre, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Progressive Multiple Sclerosis
Keywords: Balance
Dual Task
Cognitive Function
Digital Telemedicine
Wearables
Lead sponsor: Universita di Verona
Sponsor class: OTHER
Collaborators: name: Università degli Studi di Ferrara
First posted: 2024-07-03
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in the Timed Up and Go test
timeFrame: 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 outcomes:
measure: Change in the Multiple Sclerosis Functional Composite (MSFC)
timeFrame: 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)
measure: Mental workload through Electroencephalography (EEG) during Multiple Sclerosis Functional Composite Score
timeFrame: 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)
measure: Vigilance state through Electroencephalography (EEG) during Multiple Sclerosis Functional Composite Score
timeFrame: 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)
measure: Surface electromyography (EMG) during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC).
timeFrame: 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)
measure: Inertial Measurement Unit (IMU) system during the performance of the Nine Hole Peg test part of the Multiple Sclerosis Functional Composite (MSFC).
timeFrame: 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)
measure: Change in the Fatigue Severity Scale (FSS)
timeFrame: 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)
measure: Change in the Activities-specific balance confidence (ABC)
timeFrame: 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)
measure: Change in the Manual Ability Measure-36 (MAM-36)
timeFrame: 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)
measure: The number of falls in the previous month
timeFrame: 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)
measure: Timed Up and Go (TUG) test - Cognitive
timeFrame: 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)
measure: Electroencephalography (EEG) during the Timed Up and Go (TUG) test - Cognitive
timeFrame: 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)
measure: Timed Up and Go (TUG) test - Manual
timeFrame: 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)
measure: Electroencephalography (EEG) during the Timed Up and Go (TUG) test - Manual
timeFrame: 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)
measure: Change in the gait speed (cm/s)
timeFrame: 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)
measure: Change in the cadence (step/min)
timeFrame: 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)
measure: Change in the stride length (cm)
timeFrame: 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)
measure: Change in the length of the centre of pressure (CoP)
timeFrame: 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)
measure: Change in the trajectory (mm)
timeFrame: 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)
measure: Change in the sway area (mm2)
timeFrame: 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)
measure: Change in the Brief Pain Inventory (BPI)
timeFrame: 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)
measure: Change in the Hospital Anxiety and Depression Scale
timeFrame: 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)
measure: Change in the Hospital Anxiety and Depression Scale - Anxiety (HADS-A)
timeFrame: 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)
measure: Change in the Hospital Anxiety and Depression Scale - Depression (HADS-D)
timeFrame: 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)
measure: Change in the Modified Asworth Scale
timeFrame: 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)
measure: Change in the Modified Tardieu Scale
timeFrame: 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)
measure: Change in the the Multiple Sclerosis Quality Of Life-54 (MSQOL-54)
timeFrame: 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)
measure: The EuroQol five domains (EQ-5D)
timeFrame: 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)
measure: The volumes of health services
timeFrame: Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)
measure: The Multiple Sclerosis Health Resource Utilization Survey (MS-HRS)
timeFrame: Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)
measure: The TheiTA Productivity Cost Questionnaire
timeFrame: Before treatment (T0), and 24 weeks after the in-hospital treatment (T3)
measure: Change in the Clinical Global Impression (CGI)
timeFrame: 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)
measure: Changes in effective brain connectivity through Electroencephalography (EEG)
timeFrame: 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)
measure: Change in the Brief Illness Perception Questionnaire (B-IPQ)
timeFrame: 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)
measure: Change in the Multidimensional Psychological Flexibility Inventory (MPFI)
timeFrame: 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)
measure: Change in the Self-Efficacy for Multiple Sclerosis Scale (SEMS)
timeFrame: 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)
measure: Tele-healthcare Satisfaction Questionnaire-Wearable Technology
timeFrame: At the end of the 12 weeks of telerehabilitation
measure: Patients' In-home Digital Telerehabilitation training experience questionnaire
timeFrame: At the end of the 12 weeks of telerehabilitation
measure: Activity levels through Technology-based Objective Measures (TOMS)
timeFrame: 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)
measure: Number of steps through Technology-based Objective Measures (TOMS)
timeFrame: 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)
measure: Distance traveled through Technology-based Objective Measures (TOMS)
timeFrame: 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)
measure: Risk of fall assessment
timeFrame: During the 4 weeks in-hospital rehabilitation (3 days/week for 4 week - total of 10 sessions)
measure: Adverse Events
timeFrame: At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)
measure: Number of patients who accept/refuse the treatment
timeFrame: At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)
measure: Number of dropouts
timeFrame: At the end of the 12 weeks of telerehabilitation or usual care after the end of the in-hospital treatment (T2)
Other outcomes:
Locations:
city: Verona
country: Italy
facility: Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona
Study officials:
affiliation: Universita di Verona
name: Marialuisa Gandolfi
role: PRINCIPAL_INVESTIGATOR
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