NCT07310862

Brief Summary

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 will be randomized (1:1) to 4 weeks of active GSS or sham stimulation, followed by a 4-week post-treatment follow-up. 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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for not_applicable multiple-sclerosis

Timeline
11mo left

Started Mar 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress17%
Mar 2026Apr 2027

First Submitted

Initial submission to the registry

December 16, 2025

Completed
14 days until next milestone

First Posted

Study publicly available on registry

December 30, 2025

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2026

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Last Updated

February 3, 2026

Status Verified

January 1, 2026

Enrollment Period

1 year

First QC Date

December 16, 2025

Last Update Submit

January 30, 2026

Conditions

Keywords

FatigueMS fatigueCognitive FatigueMental FatigueGSSGamma Sensory StimulationVR-GSSVirtual RealityMFISNeuromodulation40Hz

Outcome Measures

Primary Outcomes (1)

  • Change in Modified Fatigue Impact Scale (MFIS) total score

    The Modified Fatigue Impact Scale (MFIS) is a 21-item patient-reported outcome assessing the impact of fatigue on physical, cognitive, and psychosocial functioning. Scores range from 0 to 84, with higher scores indicating greater fatigue impact. This outcome measures the change in MFIS total score from baseline to Week 4. Negative change values represent improvement in fatigue.

    Baseline to End of Treatment (week 4)

Secondary Outcomes (7)

  • Change in MFIS at Follow up

    Baseline to Follow-up (week 8)

  • Change in Fatigue Severity Scale (FSS)

    Baseline to End of Treatment (week 4) and Follow-up (week 8)

  • Change in Visual Analogue Scale for Mental Fatigue (VAS-MF)

    Baseline to End of Treatment (week 4) and Follow-up (week 8)

  • Change in PROMIS Fatigue Score

    Baseline to End of Treatment (week 4) and Follow-up (week 8)

  • Change in Neuro-QoL Fatigue

    Baseline to End of Treatment (week 4) and Follow-up (week 8)

  • +2 more secondary outcomes

Other Outcomes (8)

  • Change in MFIS Subscale Scores (Physical, Cognitive, Psychosocial)

    Baseline to End of Treatment (week 4) and Follow-up (week 8)

  • Cognitive Performance During Stimulation (Embedded Virtual Reality Tasks)

    Baseline through End of Treatment (week 4)

  • Treatment Acceptability Ratings

    Week 2, Week 4, and Week 8

  • +5 more other outcomes

Study Arms (2)

Gamma Sensory Stimulation

ACTIVE COMPARATOR

Participants receive Gamma Sensory Stimulation delivered through a virtual reality (VR) headset and headphones. Stimulation sessions last 30 minutes and are delivered four times per week for four weeks within standardized, engaging VR environments.

Device: Virtual Reality Gamma Sensory Stimulation

Sham Sensory Stimulation

SHAM COMPARATOR

Participants receive sham sensory stimulation delivered through a virtual reality (VR) headset and headphones. Sessions last 30 minutes and are delivered four times per week for four weeks within the same VR environments used in the active intervention.

Device: Virtual Reality Sham Sensory Stimulation

Interventions

Participants receive 30 minutes of Gamma Sensory Stimulation delivered through a virtual reality (VR) headset and headphones. Visual and auditory stimulation parameters are configured to deliver rhythmic sensory stimulation intended to engage gamma-band neural activity. Sessions occur four times per week for four weeks and are embedded within standardized VR environments.

Also known as: 40 Hz sensory stimulation, 40 Hz audiovisual stimulation, Gamma flickers, 40Hz flickers, VR-GSS
Gamma Sensory Stimulation

Participants receive 30 minutes of sham sensory stimulation delivered through a virtual reality (VR) headset and headphones. The sham intervention uses identical VR environments, session duration, and procedures as the active intervention, providing an equivalent participant experience without delivering therapeutic stimulation. Sessions occur four times per week for four weeks.

Also known as: sham sensory stimulation, sham VR-GSS
Sham Sensory Stimulation

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Be between 18 to 65 years of age (inclusive) on the day of signing informed consent.
  • 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).
  • Sufficient hearing and vision.
  • Any type of disease modifying therapy is allowed and should be stable in the last 3 months.
  • Not having received corticosteroids the previous month.
  • 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.
  • Based on the investigator's judgment, the subject should:
  • Be able to speak, read, and understand the language of the trial staff and the informed consent form;
  • Possess the ability to respond verbally to questions, follow instructions, and complete study assessments;
  • Be able to adhere to the stimulation protocol and visit schedules.

You may not qualify if:

  • Any condition or therapy impairing trial participation and assessments.
  • The presence of a relapse or use of IV steroids for any reason 3 months prior to screening visit.
  • Severe systemic diseases or history of cancer or hereditary familiar cancer.
  • Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
  • A history of seizure or epilepsy.
  • Pregnant or breastfeeding women.
  • Drug or alcohol abuse.
  • Patients with active systemic bacterial, viral or fungal infections, or known to have uncontrolled AIDS or to be HIV-positive but not receiving anti-retroviral therapy based on medical history or available clinical information at screening.
  • Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
  • 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.
  • Participation in other experimental studies within the previous 90 days prior to screening visit.
  • Patients having a pacemaker or other metal implants.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

Location

Related Publications (3)

  • 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.

    PMID: 40764732BACKGROUND
  • 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.

    PMID: 31836315BACKGROUND
  • 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.

    PMID: 39112447BACKGROUND

MeSH Terms

Conditions

Multiple SclerosisFatigueMental Fatigue

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsBehavioral SymptomsBehavior

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participants, care providers, treating investigators, and outcome assessors are blinded to treatment allocation. Active and sham stimulation are delivered through identical virtual reality content and session procedures, and no perceptual cues are provided that would allow participants or study staff to distinguish between treatment conditions. Device configuration (active or sham mode) is preset by unblinded technical personnel who are not involved in participant interaction, clinical assessments, or data analysis.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants with multiple sclerosis and significant fatigue are randomized (1:1) to receive either active Gamma Sensory Stimulation (GSS) or sham stimulation for 4 weeks in a parallel-group design.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 16, 2025

First Posted

December 30, 2025

Study Start

March 1, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

April 1, 2027

Last Updated

February 3, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

This study collects pseudonymized clinical, behavioral, and EEG data that are subject to GDPR and local data protection regulations. Because the dataset contains sensitive information that cannot be fully de-identified, individual-level data will not be made publicly available. Aggregate results may be shared in publications or upon reasonable request to the sponsor.

Locations