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

Overview

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.

Interventions

• Other Home-based Action Observation Treatment with virtual-reality for upper limb rehabilitation
  Observation of a VR scenario depicting multiple repetitions of a specific upper limb motor task belonging to typical activities of daily living, followed by mental imagination of the action observed and then by the execution of the same task, using objects provided in a kit. In each session, patients will watch 2 different videos and will perform the two corresponding actions. The time scheduled for observation, imagery and execution of each action will be of 5, 3, and 7 minutes, respectively,
• Other Home-based landscape observation with virtual-reality for upper limb rehabilitation
  Observation of virtually explorable landscapes followed by rest with eyes closed without focusing on any thought in particular and then execution of the same actions requested to VR-AOT-group. In each session, patients will explore 2 different landscapes and perform 2 different actions. The time scheduled for observation, rest and action execution will be of 5, 3, and 7 minutes, respectively, so that each session will last about 30 minutes.New actions, chosen from a dataset of 50 stimuli showing

Primary outcome measures

• Change in right hand Nine-hole peg test (9HPT) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]

Secondary outcome measures (12)

• Change in left hand Nine-hole peg test (9HPT) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in hand grip strength [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in finger tapping frequency [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Medical Research Council (MRC) scale [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Modified Ashworth Scale (MAS) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in items 1-6 of the Functional Independence Measure (FIM) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Expanded Disability Status Scale (EDSS) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Paced Auditory Serial Addition Test (PASAT) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Symbol-Digit Modalities Test (SDMT) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Montgomery-Asberg Depression Rating Scale (MADRS) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Modified Fatigue Impact Scale (MFIS) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]
• Change in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) [Time frame: Baseline, after 3 weeks of training and after a 3-month follow-up]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS San Raffaele — Milan

Publications

• 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. PMID 18077798
• 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. PMID 30084706
• 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. PMID 33910057
• 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. PMID 31115046
• 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. PMID 34782480
• 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. PMID 31352180

Identifiers

NCT: NCT05713890 · RF-2021-12374941

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗