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

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Home-based Action Observation Treatment with virtual-reality for upper limb rehabilitation
Home-based landscape observation with virtual-reality for upper limb rehabilitation
Sponsored by
IRCCS San Raffaele
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • IRCCS San RaffaeleRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

VR-AOT

VR-LO

Arm Description

Home-based Action Observation Treatment with virtual-reality for upper limb rehabilitation

Home-based landscape observation with virtual-reality for upper limb rehabilitation

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
Change in hand grip strength
Hand grip strength measured with the Jamar handheld dynamometer. Measured for left and right hand separately.
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.
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.
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.
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).
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).
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.
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.
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.
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.
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.
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).
Change in global brain volume
Normalized volumes of the brain, GM and WM will be extracted from 3D T1 MRI sequences.
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
Changes in white matter microstructural architecture
Tract-based spatial statistics (TBSS) will be used to map training-related changes of WM architecture.
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.
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.

Full Information

First Posted
January 26, 2023
Last Updated
September 26, 2023
Sponsor
IRCCS San Raffaele
Collaborators
Istituto di Neuroscienze Consiglio Nazionale delle Ricerche
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1. Study Identification

Unique Protocol Identification Number
NCT05713890
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2023 (Actual)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
July 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS San Raffaele
Collaborators
Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
Outcomes Assessor
Masking Description
The assessors (neurologists, physiotherapists and neuropsychologists) will be blinded to treatment allocation.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VR-AOT
Arm Type
Experimental
Arm Description
Home-based Action Observation Treatment with virtual-reality for upper limb rehabilitation
Arm Title
VR-LO
Arm Type
Active Comparator
Arm Description
Home-based landscape observation with virtual-reality for upper limb rehabilitation
Intervention Type
Other
Intervention Name(s)
Home-based Action Observation Treatment with virtual-reality for upper limb rehabilitation
Intervention Description
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).
Intervention Type
Other
Intervention Name(s)
Home-based landscape observation with virtual-reality for upper limb rehabilitation
Intervention Description
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).
Primary Outcome Measure Information:
Title
Change in right hand Nine-hole peg test (9HPT)
Description
Time required to complete the 9HPT, a measure of hand dexterity, with the right hand (average of two tests).
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Secondary Outcome Measure Information:
Title
Change in left hand Nine-hole peg test (9HPT)
Description
Time required to complete the 9HPT, a measure of hand dexterity, with the left hand (average of two tests).
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in hand grip strength
Description
Hand grip strength measured with the Jamar handheld dynamometer. Measured for left and right hand separately.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in finger tapping frequency
Description
Number of taps performed with the index finger in 30 seconds (average of two trials). Measured for left and right hand separately.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Medical Research Council (MRC) scale
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Modified Ashworth Scale (MAS)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in items 1-6 of the Functional Independence Measure (FIM)
Description
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).
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Expanded Disability Status Scale (EDSS)
Description
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).
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Paced Auditory Serial Addition Test (PASAT)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Symbol-Digit Modalities Test (SDMT)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Modified Fatigue Impact Scale (MFIS)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Arm Function in Multiple Sclerosis Questionnaire (AMSQ)
Description
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.
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in Multiple Sclerosis Quality of Life-54 (MSQOL-54)
Description
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).
Time Frame
Baseline, after 3 weeks of training and after a 3-month follow-up
Title
Change in global brain volume
Description
Normalized volumes of the brain, GM and WM will be extracted from 3D T1 MRI sequences.
Time Frame
Baseline and after 3 weeks of training
Title
Changes in regional gray matter volumes
Description
Tensor-based morphometry (TBM) will be used to map and compare longitudinal changes of regional GM volumes between groups
Time Frame
Baseline and after 3 weeks of training
Title
Changes in white matter microstructural architecture
Description
Tract-based spatial statistics (TBSS) will be used to map training-related changes of WM architecture.
Time Frame
Baseline and after 3 weeks of training
Title
Changes in resting state functional connectivity
Description
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.
Time Frame
Baseline and after 3 weeks of training
Title
Changes in brain activation during an object manipulation task
Description
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.
Time Frame
Baseline and after 3 weeks of training

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria A Rocca, MD
Phone
0226433019
Ext
0039
Email
rocca.mara@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Paola Valsasina, MSc
Phone
0226433944
Ext
0039
Email
valsasina.paola@hsr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria A Rocca, MD
Organizational Affiliation
IRCCS Ospedale San Raffaele
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Filippi, MD
Phone
00390226433054
Email
filippi.massimo@hsr.it
First Name & Middle Initial & Last Name & Degree
Maria A. Rocca, MD
Phone
00390226433019
Email
rocca.mara@hsr.it

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The dataset including all the data obtained from this study will be available from the Principal Investigator upon reasonable request.
IPD Sharing Time Frame
The dataset including all the data obtained from this study will be available 6 months after the publication of the results.
IPD Sharing Access Criteria
The dataset including all the data obtained from this study will be available from the Principal Investigator upon reasonable request.
Citations:
PubMed Identifier
18077798
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.
Results Reference
background
PubMed Identifier
30084706
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.
Results Reference
background
PubMed Identifier
33910057
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.
Results Reference
background
PubMed Identifier
31115046
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.
Results Reference
background
PubMed Identifier
34782480
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.
Results Reference
background
PubMed Identifier
31352180
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.
Results Reference
background

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

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