Immersive Virtual Reality and Exercise Programs in Multiple Sclerosis (ExeRVIEM II)

Benefits of a High-Intensity Exercise Program With Immersive Virtual Reality in Multiple Sclerosis: Exploratory Study

TITLE: Immersive Virtual Reality and Exercise Programs in Multiple Sclerosis

INTRODUCTION: Multiple sclerosis (MS) is a chronic neuroimmunological and degenerative disease characterized by demyelination within the central nervous system. Its clinical course involves motor impairment, sensory disturbances, cognitive dysfunction, and a progressive decline in functional independence. MS is one of the leading causes of non-traumatic disability in young adults. This highlights the considerable impact of the disease, both in terms of healthcare burden and healthcare expenditure. Within this context, therapeutic exercise has evolved from being considered potentially harmful to being recognized as a safe and effective intervention capable of improving gait, balance, cardiorespiratory fitness, fatigue, and quality of life in people with MS. A model has been proposed for prescribing and progressing exercise at different stages of MS: passive range-of-motion exercises designed for patients with the most severe symptoms, a second stage incorporating active muscle-strengthening exercises, and finally, integrated exercise programs that incorporate strength, endurance, balance, and coordination training. Evidence from systematic reviews and meta-analyses shows that structured exercise (including high-intensity protocols when performed under supervision) is safe and can improve functional outcomes. Our ExeRVIEM II project (High-Intensity Exercise Program with Immersive Virtual Reality in Multiple Sclerosis) represents a novel strategy to facilitate rehabilitation exercise programs using head-mounted virtual reality displays.

HYPOTHESIS: The ExeRVIEM II project, based on training physical function in people with MS, is feasible and safe, and could have a potential clinical impact in the motor and cognitive domains, as well as applicability in community settings, such as patient associations.

GENERAL OBJECTIVES:

1.1 To design and implement an ExeRVIEM II exercise program/protocol for people with MS.

1.2 To evaluate the feasibility and safety of the high-intensity virtual reality exercise program.

SPECIFIC OBJECTIVES:

2.1 To analyze the possible changes in disability, functional variables, cognitive domains and biomarkers in the short and medium term in people who attend a patient association and carry out the ExeRVIEM II exercise program/protocol for people with MS.

METHODOLOGY: An exploratory, pre-feasibility, single-arm, single-cohort study will be conducted at the AVEMPO patient association (Vigo, Spain). The intervention will consist of an 8-week supervised virtual rehabilitation program, with two weekly sessions on alternate days, in addition to the standard rehabilitation prescribed by the AVEMPO clinical team (physiotherapy, occupational therapy, and cognitive training sessions). An inmersive virtual reality (IVR) boxing exercise videogame will be used, administered via a virtual reality headset. In accordance with clinical guidelines for IVR, and given the exploratory nature of the study, sessions will be intentionally brief (10 minutes) to minimize cybersickness and excessive fatigue. Assessments will be conducted at baseline (week 0) and immediately after the intervention (week 8). Demographic and clinical data will also be collected, including sex, age, comorbidities, disease duration, MS subtype, and pharmacological treatment. Assessments will be conducted at the patient association and in the Neurology Department of the referral hospital. Feasibility and safety assessments will be performed at the patient association by the supervising physiotherapist, while the remaining assessments will be completed at the hospital by a neurologist specializing in MS (without blinding due to the single-group design and small setting). The content of the assessments will be:

Patient characteristics: an ad hoc registration form that will include data on age, sex, years since diagnosis, MS subtype, and pharmacological treatment.

Feasibility: Number of virtual sessions attended by each participant (adherence rate via registration sheet). Rate Perceived Effort using the modified Borg scale, which measures the level of perceived exertion on a scale of 0 to 10 from no effort to maximum effort. Usability of the virtual tool using the Sistem Usability Scale (SUS) range 0-100.

Safety: adverse events (side effects related to virtual reality exposure) using the Simulator Sickness Questionnaire (SSQ).

Level o disability: using the Expanded Disability Status Scale (EDSS). Gait will be evaluated using the 25Foot Walk Test (25FWT). Manual dexterity will be assessed using by 9-Hole Peg Test (9HPT). Cognitive domains evaluated by the Symbol Digit Modalities Test (SDMT) Axonal injury biomarker evaluated by Neurofilament light chain (sNfL) concentrations

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Physical Therapy; Virtual Reality Exposure Therapy; Rehabilitation Exercise; Exercise (EX)
• Intervention / Treatment: Other: Virtual exercise based program

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36316
      • University of Vigo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years of age.
• Confirmed diagnosis of MS.
• Stable disease with no relapse in the previous 6 weeks.
• Patients who will be take follow up by a neurologist at the referall hospital and will be members of AVEMPO.
• Ability to perform moderate exercise.
• Capacity to provide informed consent.

Exclusion Criteria:

• Comorbidities that hinder the development of the VR program
• Visual or vestibular impairment that would contraindicate VR use.
• Recent changes in disease modifying therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: ExeRVIEM II Protocol; Virtual exercise based program

Other: Virtual exercise based program; The intervention will consist of a supervised virtual rehabilitation program delivered over 8 weeks, with two sessions per week on alternating days, in addition to the standard rehabilitation prescribed by the AVEMPO clinical team (physiotherapy, occupational therapy and cognitive training sessions). An Immersive Virtual Reality boxing-based exergame executed through a VR headset will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events linked to virtual reality exposure assessed by the Simulator Sickness Questionnaire (SSQ).	SSQ assess the IVR exposure by evaluating potential associated symptoms in three broad domains: 1. oculomotor symptoms; 2. disorientation; 3. nausea. Each item is rated on a four-point scale (0 = feel nothing; 1 = a little; 2 = moderately; and 3 = very much) and the total score (maximum of 48 points) is the sum of the scores of the three subscales.	Week 8
Usability of the virtual tool assessed by System Usability Scale (SUS).	SUS consists of ten questions on a Likert-type scale. Each question is scored from 1 to 5 based on the degree of agreement or disagreement with each statement, where 5 means strongly agree and 1 means strongly disagree. The algorithm resulting from these responses generates a maximum score of 100 points.	Week 8
Number of virtual sessions attended by each participant	Adherence rate via registration sheet	up to 8 weeks
Rate perceived effort (RPE) evaluated by the modified Borg scale.	The modified Borg scale and which measures the RPE on a scale of 0-10 from no exertion (0) to the greatest possible exertion (10).	up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of disability using the Expanded Disability Status Scale (EDSS)	EDSS quantifies MS related disability on a scale from 0 (normal neurological exa-mination) to 10 (MS related death). Lower scores indicate less disability and generally, and a change of between 0.5 and 1.0 points on the EDSS scale is considered clinically significant, indicating actual progression or improvement in disability	Baseline
Level of disability using the Expanded Disability Status Scale (EDSS)	EDSS quantifies MS related disability on a scale from 0 (normal neurological exa-mination) to 10 (MS related death). Lower scores indicate less disability and generally, and a change of between 0.5 and 1.0 points on the EDSS scale is considered clinically significant, indicating actual progression or improvement in disability	Week 8
Gait evaluated by 25Foot Walk Test (25FWT)	25FWT assesses walking speed over 25 feet; shorter times reflect better gait capacity. The 25FWT is a validated, reliable measure accepted by regulatory consortia (MSOAC), predictive of disability progression, where a change greater than 20% in the time taken to walk 25 feet (7.6 meters) is considered relevant to the patient's daily life, indicating a real improvement or deterioration of their functional capacity, beyond the natural variability of the test.	Baseline
Gait evaluated by 25Foot Walk Test (25FWT)	25FWT assesses walking speed over 25 feet; shorter times reflect better gait capacity. The 25FWT is a validated, reliable measure accepted by regulatory consortia (MSOAC), predictive of disability progression, where a change greater than 20% in the time taken to walk 25 feet (7.6 meters) is considered relevant to the patient's daily life, indicating a real improvement or deterioration of their functional capacity, beyond the natural variability of the test.	Week 8
Manual dexterity assessed by 9-Hole Peg Test (9HPT)	9HPT (right and left) evaluates fine manual dexterity. Lower times indicate better performance. Reductions of approximately 20% are often considered clinically meaningful, particularly in progressive MS phenotypes. Often in clinical studies, a change of 2 seconds or more in the average test execution time is considered clinically relevant, indicating an impairment in manual dexterity and fine motor function	Baseline
Manual dexterity assessed by 9-Hole Peg Test (9HPT)	9HPT (right and left) evaluates fine manual dexterity. Lower times indicate better performance. Reductions of approximately 20% are often considered clinically meaningful, particularly in progressive MS phenotypes. Often in clinical studies, a change of 2 seconds or more in the average test execution time is considered clinically relevant, indicating an impairment in manual dexterity and fine motor function	Week 8
Cognitive domains evaluated by the Symbol Digit Modalities Test (SDMT)	SDMT assesses cognitive processing speed; higher scores indicate better performance. The SDMT is highly sensitive to cognitive impairment in MS and a variation of 4 to 5 points (or a change of at least 10% from baseline) is generally considered to indicate a real and clinically relevant change in the patient's cognitive performance	Baseline
Cognitive domains evaluated by the Symbol Digit Modalities Test (SDMT)	SDMT assesses cognitive processing speed; higher scores indicate better performance. The SDMT is highly sensitive to cognitive impairment in MS and a variation of 4 to 5 points (or a change of at least 10% from baseline) is generally considered to indicate a real and clinically relevant change in the patient's cognitive performance	Week 8
Axonal injury biomarker evaluated by Neurofilament light chain (sNfL) concentrations	sNfL expressed in serum (pg/mL) evaluates disease progression. Lower levels suggest reduced neuroaxonal damage and may reflect decreased disease activity. In this study, it was performed using an automated assay for measuring sNfL (Fujirebio).	Baseline
Axonal injury biomarker evaluated by Neurofilament light chain (sNfL) concentrations	sNfL expressed in serum (pg/mL) evaluates disease progression. Lower levels suggest reduced neuroaxonal damage and may reflect decreased disease activity. In this study, it was performed using an automated assay for measuring sNfL (Fujirebio).	Week 8

Collaborators and Investigators

• Sponsor: University of Vigo
• Collaborators: Complejo Hospitalario Universitario de Santiago; Hospital Álvaro Cunqueiro; Asociación Viguesa de Esclerosis Múltiple de Pontevedra
• Investigators: Principal Investigator: Pablo Campo Prieto, PhD, University of Vigo

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): July 1, 2025
• Study Completion (Actual): July 1, 2025

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Behavior; Multiple Sclerosis; Motor Activity
• Other Study ID Numbers: HEALTHYFIT-UVIGO 1/2026

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