An interventional study of Multidomain Home-Based Telerehabilitation Program and Self-Managed Educational Program in Multiple Sclerosis and Fatigue in Multiple Sclerosis, sponsored by IRCCS San Raffaele Roma. Active, not recruiting at 1 site in Italy. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-09.
Sponsored by IRCCS San Raffaele Roma · Not applicable, Interventional, and Other
MS-FatigueCARE is a prospective, multicenter study aimed at investigating the mechanisms underlying fatigue in people with multiple sclerosis (MS) and mild disability, and at evaluating the efficacy of a personalized home-based telerehabilitation program. Fatigue is one of the most debilitating symptoms of MS and can significantly impact daily activities and quality of life, even in individuals with low levels of neurological disability. Current assessment relies primarily on patient-reported measures, highlighting the need for objective and sensitive fatigue biomarkers.
The study comprises two complementary phases. Phase 1 is a cross-sectional observational study comparing people with relapsing-remitting MS and mild disability (EDSS score 0-3.5) with healthy controls. The objective is to investigate the relationship between perceived fatigue and objective physiological and motor parameters, focusing specifically on oxygen consumption (VO₂), the metabolic cost of walking (CW), postural control, and gait-related parameters. In participants with MS, the potential association between fatigue and Epstein-Barr virus (EBV) serological status or reactivation will also be examined.
Phase 2 is a single-blind, randomized controlled crossover study involving MS participants who completed Phase 1. Participants will be randomly assigned to either a six-week multidomain telerehabilitation program-based on non-immersive virtual reality and "serious games"-or a self-managed therapeutic education program. The telerehabilitation intervention integrates motor, cognitive, and cardiorespiratory exercises to be performed at home four times a week for 60 minutes, with remote monitoring by rehabilitation professionals. After a six-week washout period, participants will switch to the alternative intervention. The primary outcome is the energy cost of walking, measured during the 6-Minute Walking Test. Secondary outcomes include subjective fatigue, cognitive and psychological functioning, walking and balance performance, quality of life, usability, and treatment adherence, as well as instrumental measures of VO₂/VCO₂, postural control, and lower-limb kinematics.
Overall, MS-FatigueCARE aims to identify objective markers of fatigue and determine whether a personalized, multi-domain telerehabilitation approach can reduce fatigue and improve functional outcomes and quality of life for people with MS, while fostering accessible and continuous rehabilitative care.
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's planned enrollment of 120 is above the median of 50 across 2,201 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →IRCCS San Raffaele Roma is the lead sponsor of 71 studies on the registry; 25 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will first receive a 6-week multidomain home-based telerehabilitation program, delivered 4 times per week in 60-minute sessions. The intervention includes motor, cognitive, and cardiorespiratory exercises based on non-immersive virtual reality and serious games, with remote monitoring by rehabilitation professionals. After a 6-week washout period, participants will cross over to the self-managed therapeutic educational program for 6 weeks.
Other: Multidomain Home-Based Telerehabilitation Program · Other: Self-Managed Educational Program
Participants will first receive a 6-week self-managed therapeutic educational program including exercises similar to those provided in the telerehabilitation program and matched for treatment intensity and duration. Activities will be performed independently and recorded in a weekly diary. After a 6-week washout period, participants will cross over to the 6-week multidomain home-based telerehabilitation program.
Other: Multidomain Home-Based Telerehabilitation Program · Other: Self-Managed Educational Program
A 6-week multidomain home-based telerehabilitation program combining motor, cognitive, and cardiorespiratory exercises delivered through non-immersive virtual reality and serious games. Participants will perform four 60-minute sessions per week, for a minimum of 20 sessions. The program will be personalized according to individual clinical characteristics and needs. Exercises will be performed at home using a dedicated Home-Kit with connected sensors providing visual and auditory biofeedback. Rehabilitation professionals will remotely monitor participants' performance and progress and progressively adapt exercise difficulty when appropriate.
A 6-week self-managed therapeutic educational program including exercises similar to those proposed in the telerehabilitation program. The program will be adapted for people with multiple sclerosis and matched to the telerehabilitation intervention in terms of intensity and duration. Participants will perform the activities independently at home and will record completed activities in a weekly diary.
Cost of walking - CW
Cost of Walking (CW) represents the energy expenditure required to walk at a given speed and provides an index of walking efficiency. It will be assessed through cardiopulmonary exercise testing (CPET), based on oxygen consumption (VO₂), carbon dioxide production (VCO₂), and other metabolic parameters. Lower CW values indicate greater walking efficiency.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Fatigue Severity Scale (FSS)
The Fatigue Severity Scale (FSS) is a standardized self-reported questionnaire used to assess the severity of fatigue and its impact on daily activities and functional performance. It consists of 9 items, each rated on a 7-point Likert scale (1 = strongly disagree; 7 = strongly agree). The total score ranges from 9 to 63, with higher scores indicating greater fatigue severity and a more significant impact on daily functioning. The FSS is widely used in clinical practice and research to evaluate fatigue and monitor changes over time.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Modified Fatigue Impact Scale (MFIS)
The Modified Fatigue Impact Scale (MFIS) is a standardized self-reported questionnaire used to assess the impact of fatigue on daily functioning and quality of life. It consists of 21 items covering three main domains: physical, cognitive, and psychosocial functioning. Each item is rated on a 5-point Likert scale ranging from 0 (never) to 4 (almost always). The total score ranges from 0 to 84, with higher scores indicating a greater impact of fatigue on daily activities. The MFIS is widely used in clinical practice and research to evaluate fatigue-related limitations, particularly in patients with neurological disorders, and to monitor changes in fatigue impact over time.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) is a standardized self-reported assessment tool used to measure the intensity of subjective symptoms, particularly pain. It typically consists of a 100-mm horizontal line, anchored by two endpoints representing "no pain" (0) and "worst imaginable pain" (100). Participants are asked to mark the point that best reflects their perceived pain intensity. The score ranges from 0 to 100 mm, with higher scores indicating greater pain intensity. The VAS is widely used in clinical practice and research to assess pain severity, evaluate treatment effectiveness, and monitor changes in symptom intensity over time.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Montreal Cognitive Assessment Test (MoCa)
The Montreal Cognitive Assessment (MoCA) is a standardized cognitive screening tool used to assess global cognitive function and detect mild cognitive impairment. It evaluates several cognitive domains, including attention, concentration, executive functions, memory, language, visuospatial abilities, abstraction, calculation, and orientation. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. A score below 26 is commonly considered suggestive of cognitive impairment, although interpretation should account for age, education, and clinical context. The MoCA is widely used in clinical practice and research to identify cognitive deficits and monitor changes in cognitive function over time, particularly in patients with neurological disorders.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Symbol Digit Modalities Test (SDMT)
The Symbol Digit Modalities Test (SDMT) is a standardized neuropsychological assessment tool used to evaluate cognitive processing speed, attention, visual scanning, and working memory. The test requires participants to match geometric symbols with corresponding numbers using a predefined reference key within 90 seconds. It can be administered in written or oral form. The total score represents the number of correct symbol-digit substitutions, with higher scores indicating better cognitive performance. The SDMT is widely used in clinical practice and research to detect cognitive impairment and monitor changes in cognitive processing speed over time, particularly in patients with neurological disorders such as multiple sclerosis.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Paced Auditory Serial Addition Test (PASAT)
The Paced Auditory Serial Addition Test (PASAT) is a standardized neuropsychological assessment tool used to evaluate sustained and divided attention, working memory, information processing speed, and auditory processing abilities. During the test, participants listen to a sequence of single-digit numbers presented at fixed time intervals and are required to continuously add each new number to the immediately preceding one. The test is commonly administered using 3-second (PASAT-3) or 2-second (PASAT-2) intervals. Performance is assessed by the number of correct responses, with higher scores indicating better cognitive performance. In the commonly used 60-item version, scores range from 0 to 60. The PASAT is widely used in clinical practice and research to detect cognitive impairment and monitor changes in cognitive functioning over time, particularly in patients with neurological disorders such as multiple sclerosis.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
State-Trait Anxiety Inventory (STAI)
The State-Trait Anxiety Inventory (STAI) is a standardized self-reported questionnaire used to assess anxiety levels by distinguishing between state anxiety (temporary anxiety experienced in a specific situation) and trait anxiety (a relatively stable tendency to experience anxiety). It consists of 40 items divided into two subscales of 20 items each: State Anxiety (STAI-S) and Trait Anxiety (STAI-T). Each item is rated on a 4-point Likert scale, with each subscale yielding a total score ranging from 20 to 80. Higher scores indicate greater levels of anxiety. The STAI is widely used in clinical practice and research to evaluate psychological distress, assess anxiety symptoms, and monitor changes in anxiety levels over time, particularly in patients with neurological and chronic conditions.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Beck Depression Inventory (BDI)
The Beck Depression Inventory (BDI) is a standardized self-reported questionnaire used to assess the severity of depressive symptoms. It consists of 21 items evaluating cognitive, emotional, behavioral, and somatic symptoms associated with depression, including sadness, pessimism, loss of interest, fatigue, and sleep disturbances. Each item is rated on a 4-point scale ranging from 0 to 3, yielding a total score from 0 to 63, with higher scores indicating greater severity of depressive symptoms. The BDI is widely used in clinical practice and research to assess depressive symptomatology, evaluate psychological well-being, and monitor changes in depression severity over time, particularly in patients with neurological and chronic conditions.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is a standardized clinical assessment tool used to evaluate neurological impairment and disability in people with multiple sclerosis (MS). It assesses neurological function across eight Functional Systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (mental), and other neurological functions. The total score ranges from 0 to 10 in 0.5-point increments, with 0 indicating a normal neurological examination and 10 representing death due to MS. Lower scores primarily reflect neurological impairment, while higher scores increasingly emphasize walking limitations and dependence on assistance. The EDSS is widely used in clinical practice and research to assess disease severity, monitor disability progression, and evaluate treatment outcomes over time in people with multiple sclerosis.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
6 Minute Walking Test (6MWT)
The 6-Minute Walk Test (6MWT) is a standardized functional assessment tool used to evaluate walking endurance and functional exercise capacity. It measures the total distance walked in meters over a period of 6 minutes, during which participants are instructed to walk as far as possible at a self-selected pace along a standardized walkway. The total distance covered represents the primary outcome measure, with greater distances indicating better functional exercise capacity and walking endurance. The 6MWT is widely used in clinical practice and research to assess functional mobility and monitor changes in walking performance over time, particularly in patients with neurological, cardiovascular, and respiratory disorders.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Timed Up and Go test (TUG)
The Timed Up and Go (TUG) is a standardized clinical assessment tool used to evaluate functional mobility, dynamic balance, and fall risk. The test measures the time required, in seconds, for a participant to stand up from a chair, walk a distance of 3 meters at a comfortable and safe pace, turn around, walk back to the chair, and sit down. The total completion time represents the primary outcome measure, with shorter times indicating better functional mobility and balance performance. The TUG is widely used in clinical practice and research to assess mobility limitations and monitor changes in functional performance over time, particularly in patients with neurological and musculoskeletal disorders.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
TUG - Dual Task (TUG-DT)
The Timed Up and Go Dual Task (TUG-DT) is a standardized clinical assessment tool used to evaluate functional mobility, dynamic balance, and cognitive-motor interference under dual-task conditions. The test measures the time required, in seconds, for a participant to stand up from a chair, walk a distance of 3 meters, turn around, walk back to the chair, and sit down while simultaneously performing a secondary cognitive task, such as counting backward or verbal fluency. The total completion time represents the primary outcome measure, with shorter times indicating better dual-task mobility performance. The TUG-DT is widely used in clinical practice and research to assess cognitive-motor interactions, identify mobility limitations, and monitor changes in dual-task performance over time, particularly in patients with neurological disorders.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
54-item Multiple Sclerosis Quality of Life (MSQOL-54)
54-item Multiple Sclerosis Quality of Life (MSQOL-54) The 54-item Multiple Sclerosis Quality of Life Questionnaire (MSQOL-54) is a standardized self-reported assessment tool used to evaluate health-related quality of life in patients with multiple sclerosis (MS). It consists of 54 items, combining the 36-item Short Form Health Survey (SF-36) with 18 additional MS-specific items. The questionnaire assesses several domains, including physical functioning, emotional well-being, pain, fatigue, cognitive functioning, social functioning, sexual function, and overall quality of life. Domain scores are transformed to a 0-100 scale, with higher scores generally indicating better health-related quality of life. Two composite scores, the Physical Health Composite and Mental Health Composite, can also be calculated. The MSQOL-54 is widely used in clinical practice and research to assess the impact of multiple sclerosis on daily life, evaluate treatment outcomes, and monitor changes in quality of
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Sway area and Center of Pressure (CoP)
These measurements are acquired during a static balance test performed with eyes open and eyes closed; Kistler stabilometric platforms (1000 Hz, Kistler Group, Winterthur, Switzerland) will be used.
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Spatio-temporal parameters
Gait analysis with Inertial Measurement Units (IMUs)
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
Epstein-Barr virus (EBV) serological status and reactivation markers
anti-EBV antibodies and EBV DNA quantification
Time frame: Day 1 (T0 - baseline) ; After 6 weeks from day 1 (T1 - end of treatment)
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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IRCCS San Raffaele Roma