Home-based Action Observation Treatment With Virtual-reality for Arm Rehabilitation in People With Multiple Sclerosis

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05713890
• Other study ID #: RF-2021-12374941
• Status: Recruiting
• Phase: N/A
• Start date: April 6, 2023
• Est. completion date: July 2025

Study information

• Verified date: September 2023
• Source: IRCCS San Raffaele
• Contact: Maria A Rocca, MD
• Phone: 0226433019
• Email: rocca.mara[@]hsr.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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, so that each session will last about 30 minutes. New actions, chosen from a dataset of 50 stimuli showing progressively increasing levels of difficulty, will be weekly administered on the basis of patient's degree of motor impairment, to involve different manual skills. 30 minutes sessions, 5 times a week for 3 consecutive weeks (15 sessions in total).
• 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 progressively increasing levels of difficulty, will be weekly administered on the basis of patient's degree of motor impairment, to involve different manual skills. 30 minutes sessions, 5 times a week for 3 consecutive weeks (15 sessions in total).

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele	Milan

Sponsors (2)

Lead Sponsor	Collaborator
IRCCS San Raffaele	Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

Country where clinical trial is conducted

Italy, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in right hand Nine-hole peg test (9HPT)	Time required to complete the 9HPT, a measure of hand dexterity, with the right hand (average of two tests).	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in left hand Nine-hole peg test (9HPT)	Time required to complete the 9HPT, a measure of hand dexterity, with the left hand (average of two tests).	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in hand grip strength	Hand grip strength measured with the Jamar handheld dynamometer. Measured for left and right hand separately.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in finger tapping frequency	Number of taps performed with the index finger in 30 seconds (average of two trials). Measured for left and right hand separately.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Medical Research Council (MRC) scale	Segmental upper limb strength measured using the MRC scale. Scores on this scale range from 0 (no visible contraction) to 5 (normal strength). Measured for left and right upper limb separately.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Modified Ashworth Scale (MAS)	Upper limb spasticity (shoulder adductors, elbow flexors, wrist flexors and pronators) measured using the MAS. Scores in this scale range from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Measured for left and right upper limb separately.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in items 1-6 of the Functional Independence Measure (FIM)	Autonomy in upper limb-related activities of daily living measured with items 1-6 of the FIM. Each item's score ranges from 1 (total assistance needed) to 7 (complete independence).	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Expanded Disability Status Scale (EDSS)	Multiple sclerosis-related global disability and functional systems subscores. Scores in this scale range from 0 (normal neurological function) to 10 (death due to multiple sclerosis).	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Paced Auditory Serial Addition Test (PASAT)	A cognitive task that measures sustained attention and working memory. The scores of this test, ranging from 0 to 60, are corrected for age, sex and years of education. Higher scores reflect a better performance in the test.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Symbol-Digit Modalities Test (SDMT)	A cognitive task that measures information processing speed. The scores of this test, ranging from 0 to 110, are corrected for age, sex and years of education. Higher scores reflect a better performance in the test.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Montgomery-Asberg Depression Rating Scale (MADRS)	An instrument that rates the severity of depressive symptoms. It is administered by a clinician through an interview. It is composed by 10 items, each with a score ranging from 0 to 6. The overall score ranges from 0 to 60, with higher scores reflecting greater severity of depressive symptoms.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Modified Fatigue Impact Scale (MFIS)	A 21-item scale where patients rate their perceived feeling of fatigue in three subscales (physical, cognitive and psychosocial). The total score of this scale ranges from 0 to 84, with higher scores reflecting more impact of fatigue in everyday life.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Arm Function in Multiple Sclerosis Questionnaire (AMSQ)	A self-reported measure of upper limb function containing 31 items. The score of this scale ranges from 31 to 186, with higher scores indicating more limitation in hand and arm function.	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in Multiple Sclerosis Quality of Life-54 (MSQOL-54)	A health-related measure of quality of life in people with MS. It contains 54 items grouped in 12 subscales. Two summary scores can be extracted from this scale: the physical health and mental health composite scores. These scores can be derived from a weighted combination of scale scores (scale scores range from 0 to 100 and a higher scale score indicates better quality of life).	Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary	Change in global brain volume	Normalized volumes of the brain, GM and WM will be extracted from 3D T1 MRI sequences.	Baseline and after 3 weeks of training
Secondary	Changes in regional gray matter volumes	Tensor-based morphometry (TBM) will be used to map and compare longitudinal changes of regional GM volumes between groups	Baseline and after 3 weeks of training
Secondary	Changes in white matter microstructural architecture	Tract-based spatial statistics (TBSS) will be used to map training-related changes of WM architecture.	Baseline and after 3 weeks of training
Secondary	Changes in resting state functional connectivity	Independent Component Analysis will be used to decompose resting state functional MRI data into spatially independent maps and time courses, and to select the main sensory and motor functional networks of interest, as well as the Mirror Neuron System network.	Baseline and after 3 weeks of training
Secondary	Changes in brain activation during an object manipulation task	Statistical Parametric Mapping (SPM) 12 will be applied to functional MRI sequences acquired during the object manipulation task to evaluate the modifications of functional activations during this task.	Baseline and after 3 weeks of training