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NCT Number: NCT07738120

Immersive Virtual Reality and Exercise Programs in Multiple Sclerosis: ExeRVIEM III

TITLE: Immersive Virtual Reality and Exercise Programs in Multiple Sclerosis: ExeRVIEM III. 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 III project (Physiotherapy program with High-Intensity Exercise Program and Immersive Virtual Reality in Multiple Sclerosis) represents a novel strategy to facilitate rehabilitation exercise programs using head-mounted virtual reality displays. HYPOTHESIS: The ExeRVIEM III 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 III exercise program/protocol for people with MS. 1.2 To evaluate the 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 III exercise program for people with MS. METHODOLOGY: A randomized controlled trial, double-arm (experimental and control group) study will be conducted at a patient association (Santiago de Compostela, Spain). The intervention will consist of an 6-month supervised virtual rehabilitation program, with two weekly sessions on alternate days, in addition to the standard rehabilitation prescribed by the patient association clinical team (physiotherapy, occupational therapy, and cognitive training sessions). An inmersive virtual reality (IVR) body combat exercise videogame will be used, administered via a virtual reality headset. In accordance with clinical guidelines for IVR, 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 24). 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, safety, strength parameters, dual-task performance and fatigue levels assessments will be performed at the patient association by physiotherapists, while the remaining assessments will be completed at the hospital by a neurologist specializing in MS. The content of the assessments will be: Patient characteristics 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. Safety: adverse events using the Simulator Sickness Questionnaire (SSQ).Strength parameters using Five times sit to stand test (FTSST) and handgrip test. Functional mobility will be assessed using Timed and Go test (TUG) and with dual task performance using TUG-cog. Level of fatigue using the Fatigue Severity Scale (FSS). Level of disability: using the Expanded Disability Status Scale (EDSS).Gait will be evaluated using the 25Foot Walk Test (25FWT). Manual dexterity will be assessed using 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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Behavior Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Exercise Immune System Diseases Motor Activity Nervous System Diseases Physical Therapy Rehabilitation Exercise Virtual Reality Exposure Therapy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Vigo

Pontevedra, Spain

Location status: Recruiting

Location contact

Dr. Pablo Campo Prieto, PhD

CONTACT

[email protected]

+034 986801750

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 referral hospital and will be members of the patient association.
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.

Treatment and study plan

Virtual exercise based program

Other

The intervention will consist of a supervised virtual rehabilitation program delivered over 6 months, with two sessions per week on alternating days. An Immersive Virtual Reality body combat-based exergame executed through a VR headset will be used.

Standard Rehabilitation

Other

Standard rehabilitation provided by the clinical team of the patient association (physiotherapy, occupational therapy and cognitive training sessions).

Primary outcomes

Level of disability using the Expanded Disability Status Scale (EDSS)

Time frame: Baseline

EDSS quantifies Multiple sclerosis (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.
Level of disability using the Expanded Disability Status Scale (EDSS)

Time frame: week 24

EDSS quantifies Multiple sclerosis (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
Gait evaluated by 25Foot Walk Test (25FWT)

Time frame: Baseline

25FWT assesses walking speed over 25 feet; shorter times reflect better gait capacity. The 25FWT is a validated, reliable measure accepted by regulatory consortia, 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.
Gait evaluated by 25Foot Walk Test (25FWT)

Time frame: Week 24

25FWT assesses walking speed over 25 feet; shorter times reflect better gait capacity. The 25FWT is a validated, reliable measure accepted by regulatory consortia, 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.
Manual dexterity assessed by 9-Hole Peg Test (9HPT)

Time frame: Baseline

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 Multiple sclerosis (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
Manual dexterity assessed by 9-Hole Peg Test (9HPT)

Time frame: Week 24

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 Multiple sclerosis (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
Cognitive domains evaluated by the Symbol Digit Modalities Test (SDMT)

Time frame: Baseline

SDMT assesses cognitive processing speed; higher scores indicate better performance. The SDMT is highly sensitive to cognitive impairment in Multiple sclerosis (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
Cognitive domains evaluated by the Symbol Digit Modalities Test (SDMT)

Time frame: Week 24

SDMT assesses cognitive processing speed; higher scores indicate better performance. The SDMT is highly sensitive to cognitive impairment in Multiple sclerosis (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
Axonal injury biomarker evaluated by Neurofilament light chain (sNfL) concentrations

Time frame: Baseline

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.
Axonal injury biomarker evaluated by Neurofilament light chain (sNfL) concentrations

Time frame: Week 24

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.
Lower limbs strength evaluated by five times sit to stand test (FTSST)

Time frame: Baseline

FTSST is used to objectively determine measures to provide a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movement (5 repetitions standing up and sitting in a chair). Lower times indicate better performance.
Lower limbs strength evaluated by five times sit to stand test (FTSST)

Time frame: Week 24

FTSST is used to objectively determine measures to provide a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movements (5 repetitions standing up and sitting in a chair). Lower times indicate better performance
Functional mobility evaluated by five timed and go test (TUG)

Time frame: Baseline

TUG is a standardized test to assess the basic functional mobility of elderly persons and requires both static and dynamic balance. The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again. Lower times indicate better performance.
Functional mobility evaluated by five timed and go test (TUG)

Time frame: Week 24

TUG is a standardized test to assess the basic functional mobility of elderly persons and requires both static and dynamic balance. The patient is observed and timed while he rises from an arm chair, walks 3 meters, turns, walks back, and sits down again. Lower times indicate better performance.
Dual task performance evaluated by five timed and go test- cognitive (TUG-cog)

Time frame: Baseline

It involves performing the TUG physical test while simultaneously carrying out a mental task (such as counting backwards in increments of three). It is an ideal tool for assessing the ability to multitask in older adults or individuals with neurological impairment. Lower times indicate better performance.
Dual task performance evaluated by five timed and go test- cognitive (TUG-cog)

Time frame: Week 24

It involves performing the TUG physical test while simultaneously carrying out a mental task (such as counting backwards in increments of three). It is an ideal tool for assessing the ability to multitask in older adults or individuals with neurological impairment. Lower times better performance.
Upper limbs strength evaluated by handgrip test

Time frame: Baseline

A handgrip strength test measures the maximum force your hand and forearm muscles can make. It acts as a key indicator for overall body strength and healthy aging. Higher scores indicates better performance.
Upper limbs strength evaluated by handgrip test

Time frame: Week 24

A handgrip strength test measures the maximum force your hand and forearm muscles can make. It acts as a key indicator for overall body strength and healthy aging. Higher scores indicates better performance.
Levels of fatigue evaluated with The Fatigue Severity Scale (FSS)

Time frame: Baseline

The FSS is a questionnaire with 9 questions that measures the extreme fatigue that affects many people with multiple sclerosis. Lower scores in the scale indicate less fatigue.
Levels of fatigue evaluated with The Fatigue Severity Scale (FSS)

Time frame: Week 24

The FSS is a questionnaire with 9 questions that measures the extreme fatigue that affects many people with multiple sclerosis. Lower scores in the scale indicate less fatigue.

Study contacts

Contact information is provided by the study sponsor or research team.

Pablo Campo-Prieto, PhD

CONTACT

[email protected]

986801770

Sponsors and collaborators

Lead sponsor

University of Vigo

Other

Collaborators

ACEM Asociación Compostelá de Esclerose Múltiple, Párkinson e ELA
Complejo Hospitalario Universitario de Santiago

Registry information

Official study title

Effects of a Physiotherapy Program With High-Intensity Exercise and Immersive Virtual Reality in Multiple Sclerosis: Randomized Controlled Trial

Acronym: ExeRVIEM III

Important dates

Study start: 2025
Primary completion: 2026
Study completion: 2026
First posted: Jul 31, 2026
Registry last updated: Jul 31, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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