Virtual Reality - Gamma Sensory Stimulation for Improving Fatigue in People With Multiple Sclerosis

NCT ID: NCT07310862

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2027-03-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a double-blind, parallel, randomized, sham-controlled pilot study evaluating the safety, feasibility, and efficacy of Gamma Sensory Stimulation (GSS) delivered via a Virtual Reality (VR) headset in individuals with Multiple Sclerosis (MS) who experience moderate to severe fatigue. Participants demonstrating significant neural entrainment to 40 Hz audiovisual stimulation will be randomized (1:1) to 8 weeks of active GSS or sham stimulation. The primary objective is to determine whether GSS reduces fatigue, measured by the Modified Fatigue Impact Scale (MFIS). Secondary outcomes include additional fatigue scales, cognitive performance, quality-of-life measures, tolerability and safety.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Gamma Sensory Stimulation (GSS) is a non-invasive audiovisual neuromodulation method that delivers synchronized 40 Hz stimulation to engage gamma-band neural oscillations. Gamma-frequency activity is implicated in cognitive processes and large-scale network synchrony, all of which are disrupted in people with Multiple Sclerosis (MS) who experience fatigue. Prior research suggests that gamma entrainment may enhance neural connectivity and improve cognitive and functional outcomes.

This single-center, double-blind, randomized, sham-controlled pilot study investigates whether 8 weeks of GSS delivered through an immersive Virtual Reality (VR) system can reduce fatigue in individuals with MS. Participants with significant fatigue and demonstrable neural entrainment to 40 Hz audiovisual stimulation will be randomized in a 1:1 ratio to receive either active GSS or sham stimulation embedded in matched VR content. The intervention consists of 30-minute in-lab sessions, 5 times per week during the first 4 weeks, followed by 3 times per week for an additional 4 weeks.

The primary endpoint is the change in Modified Fatigue Impact Scale (MFIS) total score from baseline to Week 8. Secondary endpoints include changes in other validated measures of fatigue (FSS, VAS-Mental Fatigue, PROMIS Fatigue), cognitive performance assessed by the Symbol Digit Modalities Test (SDMT), and quality-of-life measures (Neuro-QoL Fatigue, PROMIS Fatigue). Exploratory outcomes include MFIS subscales, daily fatigue ratings, and treatment acceptability. Safety and tolerability will be assessed through monitoring of adverse events, session attendance, and retention. EEG will be used at baseline and Week 8 to characterize neural responses to stimulation in the gamma-band.

This pilot investigation aims to generate preliminary efficacy and safety data to inform future multisite trials evaluating VR-GSS as an at-home therapeutic approach for MS-related fatigue.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Multiple Sclerosis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Fatigue MS fatigue Cognitive Fatigue Mental Fatigue GSS Gamma Sensory Stimulation VR-GSS Virtual Reality MFIS Neuromodulation 40Hz

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants with multiple sclerosis and significant fatigue are randomized (1:1) to receive either active Gamma Sensory Stimulation (GSS) or sham stimulation for 8 weeks in a parallel-group design.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participants, care providers, treating investigators, and outcome assessors are blinded to treatment allocation. Sham stimulation uses aperiodic audiovisual flicker embedded in identical VR content to prevent perceptual differentiation from active GSS. Device configuration (active vs sham) is preset by an unblinded technician not involved in assessments.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Gamma Sensory Stimulation

Participants receive 30 minutes of 40 Hz audiovisual stimulation delivered via a VR headset and headphones. Visual brightness and auditory amplitude oscillate at 40 Hz. The content is embedded in engaging VR environments.

Group Type ACTIVE_COMPARATOR

Virtual Reality Gamma Sensory Stimulation

Intervention Type DEVICE

Participants receive 30 minutes of Gamma Sensory Stimulation delivered through a VR headset and headphones. Visual brightness and auditory amplitude are modulated synchronously at 40 Hz to induce gamma-band neural entrainment. Sessions occur 5 times per week for 4 weeks, then 3 times per week for 4 additional weeks. Stimulation is embedded within an engaging VR environments.

Sham Sensory Stimulation

Participants receive 30 minutes of sham audiovisual stimulation delivered via a VR headset and headphones. VR content is matched for appearance and engagement to the active condition, but audiovisual signals are modulated in an aperiodic, non-rhythmic pattern rather than periodic fluctuations at 40 Hz, to prevent gamma-band neural entrainment.

Group Type SHAM_COMPARATOR

Virtual Reality Sham Sensory Stimulation

Intervention Type DEVICE

Participants receive 30 minutes of Sham Sensory Stimulation delivered through a VR headset and headphones. Visual brightness and auditory amplitude are modulated synchronously but at an irregular rate. Sessions occur 5 times per week for 4 weeks, then 3 times per week for 4 additional weeks. Stimulation is embedded within the same engaging VR environments presented in the active intervention.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Virtual Reality Gamma Sensory Stimulation

Participants receive 30 minutes of Gamma Sensory Stimulation delivered through a VR headset and headphones. Visual brightness and auditory amplitude are modulated synchronously at 40 Hz to induce gamma-band neural entrainment. Sessions occur 5 times per week for 4 weeks, then 3 times per week for 4 additional weeks. Stimulation is embedded within an engaging VR environments.

Intervention Type DEVICE

Virtual Reality Sham Sensory Stimulation

Participants receive 30 minutes of Sham Sensory Stimulation delivered through a VR headset and headphones. Visual brightness and auditory amplitude are modulated synchronously but at an irregular rate. Sessions occur 5 times per week for 4 weeks, then 3 times per week for 4 additional weeks. Stimulation is embedded within the same engaging VR environments presented in the active intervention.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

40 Hz sensory stimulation 40 Hz audiovisual stimulation Gamma flickers 40Hz flickers VR-GSS Aperiodic flicker sham sensory stimulation sham VR-GSS

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Be between 21 to 65 years of age (inclusive) on the day of signing informed consent.
2. Have MS (McDonald criteria 2017) with Modified Fatigue Impact Scale (MFIS) score greater than 33 OR fatigue greater than 4 (out of 7) on the Fatigue Severity Scale (FSS).
3. Significant neural entrainment to 40Hz audiovisual stimuli.
4. Any type of disease modifying therapy is allowed and should be stable in the last 3 months.
5. Not having received corticosteroids the previous month.
6. Each subject must sign the informed consent form, in accordance with local requirements, after the scope and nature of the investigation have been explained to the subject, and before Screening assessments.
7. Based on the investigator's judgment, the subject should:

1. Be able to speak, read, and understand the language of the trial staff and the informed consent form;
2. Possess the ability to respond verbally to questions, follow instructions, and complete study assessments;
3. Be able to adhere to the stimulation protocol and visit schedules.
8. Women of child-bearing potential\* must have a negative urine pregnancy test before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include intrauterine device, implant, patch or pill, bilateral tubal occlusion, vasectomized partner and sexual abstinence.

Exclusion Criteria

1. Any condition or therapy impairing trial participation and assessments.
2. The presence of a relapse or use of IV steroids for any reason 3 months prior to screening visit.
3. Severe systemic diseases or history of cancer or hereditary familiar cancer.
4. Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
5. A history of seizure or epilepsy including family history of seizure or epilepsy
6. Pregnant or breastfeeding women.
7. Drug or alcohol abuse.
8. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
9. Ongoing known bacterial, viral or fungal infection (with the exception of onychomycosis and dermatomycosis), positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
10. Patients with a known history of syphilis or tuberculosis or test positive for syphilis (positive rapid plasma regain, RPR) or tuberculosis (positive skin test) at screening. Active or latent tuberculosis (TB).
11. Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
12. Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study.
13. Participation in other experimental studies within the previous 90 days prior to screening visit.
14. Patients having a pacemaker or other metal implants.
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Parc de Salut Mar

OTHER

Sponsor Role collaborator

Clarity Health Technologies, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hospital del Mar

Barcelona, Barcelona, Spain

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Spain

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Carolina Reis, PhD

Role: CONTACT

Phone: +33781261622

Email: [email protected]

Sergi Navarro, MSc

Role: CONTACT

Phone: +34629116058

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Delia Paola Ceballos, MD

Role: primary

Villoslada Pablo, MD, pHD

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

Reis C, Azizollahi H, Headley G, Navarro S, Hanslmayr S, Clouter A, Zanto TP, Certain R. VR-based gamma sensory stimulation: a pilot feasibility study. Sci Rep. 2025 Aug 5;15(1):28491. doi: 10.1038/s41598-025-13725-6.

Reference Type BACKGROUND
PMID: 40764732 (View on PubMed)

Adaikkan C, Tsai LH. Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities. Trends Neurosci. 2020 Jan;43(1):24-41. doi: 10.1016/j.tins.2019.11.001. Epub 2019 Dec 10.

Reference Type BACKGROUND
PMID: 31836315 (View on PubMed)

Rodrigues-Amorim D, Bozzelli PL, Kim T, Liu L, Gibson O, Yang CY, Murdock MH, Galiana-Melendez F, Schatz B, Davison A, Islam MR, Shin Park D, Raju RM, Abdurrob F, Nelson AJ, Min Ren J, Yang V, Stokes MP, Tsai LH. Multisensory gamma stimulation mitigates the effects of demyelination induced by cuprizone in male mice. Nat Commun. 2024 Aug 8;15(1):6744. doi: 10.1038/s41467-024-51003-7.

Reference Type BACKGROUND
PMID: 39112447 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CHT0002

Identifier Type: -

Identifier Source: org_study_id