Clinical trial NCT05713890: Home-based Action Observation Treatment With Virtual-reality for Arm Rehabilitation in People With Multiple Sclerosis
Official title: An Integrated and Home-based Motor Rehabilitation Combining Virtual Reality and Action Observation Treatment in People With Multiple Sclerosis: a Clinical and Neuroimaging Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Istituto di Neuroscienze Consiglio Nazionale delle Ricerche
First posted: 2023-02-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, controlled, single-blinded, parallel study. A total sample size of 60 PwMS is planned, with 30 participants randomly assigned to each of the treatment arms (ratio 1:1) through a computer-generated list managed by a physician external to the study.
Primary purpose: TREATMENT

Brief summary: Action Observation Treatment (AOT) is a rehabilitative strategy which has been proposed as a promising approach to improve motor performance in neurological conditions, including multiple sclerosis (MS).

In this clinical trial, the investigators aim to explore the role of a home-based AOT with virtual reality (VR) in improving upper limb motor function in people with MS (PwMS). The objectives are:

* To compare the effects of home-based VR-AOT versus VR-landscape observation (LO) on upper limb motor performance;
* To measure brain network functional changes (functional plasticity) and structural variations of gray matter (GM) and white matter (WM) (structural plasticity) using advanced magnetic resonance imaging (MRI) techniques following VR-AOT and VR-LO;
* To study the correlations between MRI changes and clinical improvements and the predictors of VR-AOT efficacy.

All participants will undergo treatment sessions for 3 weeks (5 consecutive days/week, total=15 sessions lasting 30 minutes each). Those in the VR-AOT group will observe, imagine and execute two upper limb motor tasks in each session. Those in the VR-LO group will perform the same tasks, but they will observe inanimate landscapes beforehand instead.


Eligibility criteria: Inclusion Criteria:

* Age 18-65 years;
* Diagnosis of MS according to 2017 revised McDonald criteria;
* Ability to understand the purpose and risks of the study and provide signed informed consent;
* Ability to remotely perform VR-AOT;
* Right pre-morbid handedness (EHI\>50);
* Muscle strength deficit involving the right upper limb (≥1 point decrease of MRC scale);
* Presence of activity limitation of the right hand (need of adaptations, supervision or help by another person for the execution of daily living activities according to items 1-6 of the FIM);
* EDSS score 2.0-7.0 (inclusive);
* Cerebellar functional system score of the EDSS ≤1;
* Baseline 9HPT score \>21 seconds and \<180 seconds.

Exclusion Criteria:

* MRI contraindications;
* Significant visual deficits not allowing to observe VR stimuli;
* Moderate to severe pain disturbances (VAS≥4);
* Concomitant neuro-psychiatric or systemic diseases (other than MS);
* Clinical relapses or steroid treatment in the past 3 months;
* Modification of symptomatic treatment or botulin toxin injection in the upper limb in the past 3 months;
* Stable disease-modifying treatment for MS for ≤6 months;
* Rehabilitation treatment in the past 3 months.

Primary outcomes:
measure: Change in right hand Nine-hole peg test (9HPT)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary outcomes:
measure: Change in left hand Nine-hole peg test (9HPT)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in hand grip strength
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in finger tapping frequency
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Medical Research Council (MRC) scale
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Modified Ashworth Scale (MAS)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in items 1-6 of the Functional Independence Measure (FIM)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Expanded Disability Status Scale (EDSS)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Paced Auditory Serial Addition Test (PASAT)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Symbol-Digit Modalities Test (SDMT)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Modified Fatigue Impact Scale (MFIS)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Arm Function in Multiple Sclerosis Questionnaire (AMSQ)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in Multiple Sclerosis Quality of Life-54 (MSQOL-54)
timeFrame: Baseline, after 3 weeks of training and after a 3-month follow-up
measure: Change in global brain volume
timeFrame: Baseline and after 3 weeks of training
measure: Changes in regional gray matter volumes
timeFrame: Baseline and after 3 weeks of training
measure: Changes in white matter microstructural architecture
timeFrame: Baseline and after 3 weeks of training
measure: Changes in resting state functional connectivity
timeFrame: Baseline and after 3 weeks of training
measure: Changes in brain activation during an object manipulation task
timeFrame: Baseline and after 3 weeks of training
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Maria A Rocca, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rocca MA, Tortorella P, Ceccarelli A, Falini A, Tango D, Scotti G, Comi G, Filippi M. The "mirror-neuron system" in MS: A 3 tesla fMRI study. Neurology. 2008 Jan 22;70(4):255-62. doi: 10.1212/01.wnl.0000284667.29375.7e. Epub 2007 Dec 12.
citation: Rocca MA, Meani A, Fumagalli S, Pagani E, Gatti R, Martinelli-Boneschi F, Esposito F, Preziosa P, Cordani C, Comi G, Filippi M. Functional and structural plasticity following action observation training in multiple sclerosis. Mult Scler. 2019 Oct;25(11):1472-1487. doi: 10.1177/1352458518792771. Epub 2018 Aug 7.
citation: Rizzolatti G, Fabbri-Destro M, Nuara A, Gatti R, Avanzini P. The role of mirror mechanism in the recovery, maintenance, and acquisition of motor abilities. Neurosci Biobehav Rev. 2021 Aug;127:404-423. doi: 10.1016/j.neubiorev.2021.04.024. Epub 2021 Apr 25.
citation: Nuara A, Avanzini P, Rizzolatti G, Fabbri-Destro M. Efficacy of a home-based platform for child-to-child interaction on hand motor function in unilateral cerebral palsy. Dev Med Child Neurol. 2019 Nov;61(11):1314-1322. doi: 10.1111/dmcn.14262. Epub 2019 May 21.
citation: De Marco D, Scalona E, Bazzini MC, Nuara A, Taglione E, Lopomo NF, Rizzolatti G, Fabbri-Destro M, Avanzini P. Observation of others' actions during limb immobilization prevents the subsequent decay of motor performance. Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):e2025979118. doi: 10.1073/pnas.2025979118.
citation: Jonsdottir J, Perini G, Ascolese A, Bowman T, Montesano A, Lawo M, Bertoni R. Unilateral arm rehabilitation for persons with multiple sclerosis using serious games in a virtual reality approach: Bilateral treatment effect? Mult Scler Relat Disord. 2019 Oct;35:76-82. doi: 10.1016/j.msard.2019.07.010. Epub 2019 Jul 20.