Telerehabilitation in Multiple Sclerosis

Study Overview
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Brief Summary
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The main aim of the study is to evaluate the efficacy of the Virtual Reality Rehabilitation System (VRRS, Khymeia) compared to usual care treatment for patients with MS at home. The effects of the intervention on outcome variables will be assessed using a randomized controlled trial design with a comparison group receiving usual care training. The investigators will assess the effect of VRRS system on the quality of life, motor, and cognitive abilities. (Phase I) In the second phase of the present study we aim to evaluate the effects induced by the treatment of active (anodal) transcranial Direct Current Stimulation (tDCS) applied to the left dorsolateral prefrontal cortex (lDLPFC) combined with VRRS compared to placebo tDCS stimulation combined with VRRS. The effects of the intervention patient-relevant outcomes will be assessed using a randomized controlled trial design with four groups. The investigators will assess the effect of VRRS system on patient-relevant outcomes motor, cognitive and participation. (Phase II)

Official Title
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The Italian Network of Telerehabilitation: Evaluation of Telerehabilitation System for Continuum of Care in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Behavioral: VRRS Khymeia
* Behavioral: Usual care program
* Behavioral: VRRS Khymeia plus active tDCS
* Behavioral: VRRS Khymeia plus placebo tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Multiple Sclerosis (RR and SP) based on McDonald criteria Education ≥ 8 ages Italian mother language Right-handedness Use of corticosteroids for three months prior to the study, having and no acute exacerbations of symptoms within three months of the study. Exclusion Criteria: Existence of visual acuity and acoustic perception problems, to prevent performance of VRRS activities Relapses next to the time of enrolment (3 months) EDSS > 6.5.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VRRS Khymeia<br>The group will receive a kit home-based (a tablet home, an exercise equipment, access to a daily individualized training program). The exercise program will be remotely charged by therapist on the patient's computer. Each patient's performed session will be reviewed remotely by the therapist. | Behavioral: VRRS Khymeia<br>* Participants will receive an individualized exercise program set up by the therapist. The intervention applied to the experimental group will consist of 30 sessions of Khymeia VRRS training distributed in five sessions for week, each lasting 45 minutes. Each session is constructed by alternating physical with cognitive activities. The sessions will initially be tailored to the patient's baseline characteristics. Remotely, the therapist will then adjust the participant's exercise program as appropriate, by changing exercises, level of difficulty or number of repetitions.<br>|
| Active Comparator: Usual care program<br>The usual care group will have written, home-based exercise program, provided to them at an initial face-to-face assessment. | Behavioral: Usual care program<br>* The usual care group will have written, home-based exercise program, provided to them at an initial face-to-face assessment.<br>|
| Experimental: VRRS Khymeia plus active tDCS<br>The group will receive 5 sessions each lasting 45 minutes of an individualized home-based VRRS training combined with active (anodal) tDCS applied to the left dorsolateral prefrontal cortex over 1 week, followed by 5 weeks of home-based VRRS training | Behavioral: VRRS Khymeia plus active tDCS<br>* Participants will receive 5 sessions each lasting 45 minutes of an individualized home-based VRRS training combined with active (anodal) tDCS applied to the left dorsolateral prefrontal cortex over 1 week, followed by 5 weeks of home-based VRRS training. The sessions of VRRS will initially be tailored to the patient's baseline characteristics. Remotely, the therapist will then adjust the participant's exercise program as appropriate, by changing exercises, level of difficulty or number of repetitions.<br>|
| Active Comparator: VRRS Khymeia plus placebo tDCS<br>The group will receive 5 sessions of an individualized home-based VRRS training combined with placebo tDCS applied to the left dorsolateral prefrontal cortex over 1 week, followed by 5 weeks of home-based VRRS training | Behavioral: VRRS Khymeia plus placebo tDCS<br>* Participants will receive 5 sessions each lasting 45 minutes of an individualized home-based VRRS training combined with active (anodal) tDCS applied to the left dorsolateral prefrontal cortex over 1 week, followed by 5 weeks of home-based VRRS training. The sessions of VRRS will initially be tailored to the patient's baseline characteristics. Remotely, the therapist will then adjust the participant's exercise program as appropriate, by changing exercises, level of difficulty or number of repetitions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in measure of quality of life | Quality of life will be measured by 54-item Multiple Sclerosis Quality of Life (MSQOL-54) questionnaire 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. In addition, there are 12 subscales: 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. There are also two single-item measures: satisfaction with sexual function and change in health. Administration forms and scoring instructions can be downloaded (https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/MSQOL54_995.pdf ). Higher values represent a better outcome | Baseline up to 6 weeks and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in balance | Mini-Balance Evalutation System (mini-BES) Test | Baseline up to 6 weeks and 6 months | 
| Change in gait | 12-item Multiple Sclerosis Walking Scale | Baseline up to 6 weeks and 6 months | 
| Change gross manual dexterity | Box and Block Test | Baseline up to 6 weeks and 6 months | 
| Change in global cognitive status | Montreal Cognitive Assessment (MoCA) test | Baseline up to 6 weeks and 6 months | 
| Change cognitive status | Symbol Digit Modalities Test (Form Brief Repeatable Battery of Neuropsychological Tests ) | Baseline up to 6 weeks and 6 months | 
| Change in fatigue | Fatigue Severity Scale A questionnaire with 9 items (questions) Grading of each FSS item ranges from 1 to 7, where 1 indicates strong disagreement and 7 strong agreement, and the final score represents the mean value of the 9 items Higher values represent a worse outcome | Baseline up to 6 weeks and 6 months | 
| Change in Emotional Traits | The Regulatory Emotional Self-Efficacy (RESE) scale The RESE scale assesses self-efficacy in expressing positive emotions and self-efficacy in managing negative emotions. With this scale, participants rate (ranging from 1 [not well at all] to 5 [very well]) their capability to manage their emotional life. RESE scale consists of 12 items and are calculated 3 scores: 1) self-efficacy in expressing positive emotions (POS) score; 2)self-efficacy in managing negative emotions (NEG) score; 3)self-efficacy in managing despondency/distress (DES) score Higher values within each score represent a better outcome | Baseline up to 6 weeks and 6 months | 
| Change in Behavioral (depression) | Beck Depression Inventory | Baseline up to 6 weeks and 6 months | 
| Change in Behavioral (anxiety) | State-trait anxiety inventory | Baseline up to 6 weeks and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Telerehabilitation, Virtual reality, Quality of life, transcranial Direct Current Stimulation