VR-based Action Observation Treatment for Upper Limb Rehabilitation in Stroke: a Multimodal Study.

The Upper-limb Functional Rehabilitation in Chronic Stroke Patients: From Neuroimaging and Bio-humoral Biomarkers of a Personalized Action Observation Treatment Based on Virtual Reality to a Maximized and Predictable Rehabilitative Outcome.

The loss of upper-limb motor functioning due to ischemic stroke has a negative impact on quality of life of patients. Action Observation Treatment (AOT), recently developed based on the mirror mechanism functioning, has proved effective in promoting plasticity into the motor system, ultimately boosting the motor recovery. The use of virtual reality further empowers the effectiveness of AOT, making the visual experience more first-person, and thus more realistic. A complete picture of the neurobiological mechanisms underlying AOT effectiveness is lacking to date, including the neuroradiological and biohumoral markers modulated by AOT, and their role in predicting the clinical outcome. Starting from these premises, the investigators propose a study aiming at evaluating the AOT effectiveness in post-stroke patients, and at identifying the biomarkers indexing the motor recovery process.

Sixty patients affected by ischemic stroke will be enrolled at Humanitas Clinical and Research Center IRCCS (ICH) Stroke Unit will be included and randomized in the following groups:

• VR-AOT: experimental group, observing actions in virtual reality
• VR-LO: control groups, observing a matched dose of videos depicting landscapes in virtual reality.

Clinical, neuroimaging and biohumoral evaluations, performed at Screening (Ts), Basal visit (T0), end-of-treatment (T1), 2 months follow up (FU-2), will include the following endpoints: Fugl-Meyer upper extremity motor scale (FM-UE); Nine-hole-peg test; Box and block test; Modified Ashworth scale; MRC; Pain Numeric-rating-scale; Functional Independence measure.

Patients will undergo treatment sessions for 6 weeks (5 days/week). VR-AOT patients will observe in virtual reality -rehearse and execute specific upper limb motor task belonging to activities of daily living. VR-LO participants will observe virtually explorable landscapes lasting for a matched duration. Then, participants will be asked to actively perform the same set of hand actions requested to VR-AOT experimental groups.

An intention-to-treat (ITT) analysis will be performed, using rmANOVA, minimal clinically important difference (MCID) in clinical outcomes, and chi-square test. For the primary endpoints, a two-arms rmANOVA with time as within-subject factor (3 levels: T0, T1, FU2) and group (VR-AOT vs VR-LO) as between-subjects factor will be conducted. The same approach will be adopted for secondary outcome measures. Subsequently, the effect of clinical, neuroradiological and biohumoral baseline features will be tested as regressors on the primary outcome variations via linear or ranked regression models. Significance will be set at 5%, and adjusted for MC.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Behavioral: Action Observation and following Action Execution; Behavioral: Landscape Observation and following Action Execution

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Parma, Italy, 43125
    • Recruiting
    • Pietro Avanzini
    • Contact: Pietro Avanzini, PhD; Phone Number: +39 0521 903877; Email: pietro.avanzini@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age>18
• Ischemic stroke in the territory of middle cerebral artery (MCA, lesion extension lower than half of its territory) or lacunar stroke
• MRC score 2-4 in at least one segment of the affected limb
• Modified Rankin Scale (mRS) prior to stroke ≤ 2
• Able to perform study requirements
• Able to give informed consent according to ICH/ GCP, and national/local regulations

Exclusion Criteria:

• Presence of global aphasia
• History of seizures
• Posterior circulation stroke
• Significant ipovisus
• Moderate-to severe neglect
• Cognitive impairment or language barriers
• Psychiatric comorbidities
• Drug or alcohol abuse
• Autoimmune disease
• Contraindication to perform MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VR-AOT; Experimental group, observing actions in virtual reality	Behavioral: Action Observation and following Action Execution; VR-AOT patients will observe, rehearse and execute specific upper limb motor task belonging to activities of daily living.
Other: VR-LO; Control group, observing a matched dose of videos depicting landscapes in virtual reality	Behavioral: Landscape Observation and following Action Execution; VR-LO participants will observe virtually explorable landscapes lasting for a matched duration. Then, they will be asked to actively perform the same set of hand actions requested to VR-AOT experimental groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Fugl-Meyer upper extremity motor scale at 6 weeks	Stroke-specific, performance-based, impairment index (range 0-66, higher values indicate a better performance)	Six weeks from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline Nine-hole-peg test at 6 weeks	Standardized, quantitative test of upper extremity function	Six weeks from baseline
Change from baseline Nine-hole-peg test at 2 months	Standardized, quantitative test of upper extremity function	Two months from baseline
Change from baseline Box and block test at 6 weeks	Unilateral gross manual dexterity measure	Six weeks from baseline
Change from baseline Box and block test at 2 months	Unilateral gross manual dexterity measure	Two months from baseline
Change from baseline Modified Ashworth Scale at 6 weeks	Spasticity measure, evaluating limb's tone responsiveness to passive mobilization (Range: 0-4, higher values indicates higher degree of spasticity)	Six weeks from baseline
Change from baseline Modified Ashworth Scale at 2 months	Spasticity measure, evaluating limb's tone responsiveness to passive mobilization (Range: 0-4, higher values indicates higher degree of spasticity)	Two months from baseline
Change from baseline Functional Independence Measure at 6 weeks	Questionnaire measuring the independence in Activities of Daily Living (ADL). (Range: 18-126, higher values indicate an higher degree of functional independence)	Six weeks from baseline
Change from baseline Functional Independence Measure at 2 months	Questionnaire measuring the independence in Activities of Daily Living (ADL). (Range: 18-126, higher values indicate an higher degree of functional independence)	Two months from baseline
Change from baseline Fugl-Meyer upper extremity motor scale at 2 months	Stroke-specific, performance-based, impairment index (range 0-66, higher values indicate a better performance)	Two months from baseline

Collaborators and Investigators

• Sponsor: CNR Institute of Neuroscience, Parma
• Collaborators: Humanitas Hospital, Italy

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): April 30, 2025

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2023
• Last Update Submitted That Met QC Criteria: March 10, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: VR-AOT-GR-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No