Virtual Reality - Gamma Sensory Stimulation for Improving Fatigue in People With Multiple Sclerosis (VR-GSS)

January 30, 2026 updated by: Clarity Health Technologies, Inc

Gamma Sensory Stimulation (GSS) for Improving Fatigue in People With Multiple Sclerosis

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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 processing and large-scale network coordination, which may be disrupted in people with Multiple Sclerosis (MS), particularly in those experiencing fatigue. Prior research suggests that gamma-frequency entrainment may modulate neural network activity and support functional outcomes.

This single-center, double-blind, randomized, sham-controlled pilot study investigates whether 4 weeks of GSS delivered through an immersive Virtual Reality (VR) system can reduce fatigue in individuals with MS. Participants with moderate to severe fatigue 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 16 in-lab stimulation sessions delivered over 4 weeks (4 sessions per week). Each session includes 30 minutes of active stimulation within a standardized VR experience.

The primary endpoint is the change in Modified Fatigue Impact Scale (MFIS) total score from baseline to End of Treatment (Week 4). Secondary endpoints include changes from baseline to End of Treatment (Week 4) and follow-up (Week 8) in additional validated fatigue measures (Fatigue Severity Scale, Visual Analogue Scale for Mental Fatigue, PROMIS Fatigue), cognitive performance assessed by the Symbol Digit Modalities Test (SDMT), quality-of-life measures (Neuro-QoL Fatigue), and the rate of change in Daily Fatigue Severity (DFS) across the treatment period. Exploratory outcomes include MFIS subscale scores, variability in daily fatigue ratings, embedded cognitive task performance during stimulation, and treatment acceptability.

Safety and tolerability will be assessed through monitoring of adverse events, session attendance, and retention. Electroencephalography (EEG) will be collected at baseline and at End of Treatment (Week 4) for exploratory characterization of neural responses to gamma-frequency stimulation.

This pilot investigation aims to generate preliminary safety, feasibility, and efficacy data to inform future multisite studies evaluating VR-based GSS as a potential at-home therapeutic approach for MS-related fatigue.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Be between 18 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. Sufficient hearing and vision.
  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.
  6. Pregnant or breastfeeding women.
  7. Drug or alcohol abuse.
  8. 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.
  9. Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
  10. 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.
  11. Participation in other experimental studies within the previous 90 days prior to screening visit.
  12. Patients having a pacemaker or other metal implants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Gamma Sensory Stimulation
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
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.
Other Names:
  • 40 Hz sensory stimulation
  • 40 Hz audiovisual stimulation
  • Gamma flickers
  • 40Hz flickers
  • VR-GSS
Sham Comparator: Sham Sensory Stimulation
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
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.
Other Names:
  • sham sensory stimulation
  • sham VR-GSS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Modified Fatigue Impact Scale (MFIS) total score
Time Frame: Baseline to End of Treatment (week 4)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in MFIS at Follow up
Time Frame: Baseline to Follow-up (week 8)
MFIS is a 21-item patient-reported fatigue impact scale (range 0-84; higher scores indicate greater fatigue). This outcome assesses change in total MFIS score from baseline to follow-up assessment (Week 8).
Baseline to Follow-up (week 8)
Change in Fatigue Severity Scale (FSS)
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
The Fatigue Severity Scale (FSS) is a 9-item questionnaire assessing the severity and functional impact of fatigue on daily activities. Each item is scored 1-7; the final score is the mean of all items, with higher scores indicating more severe fatigue. This outcome reflects change in FSS score from baseline to Week 4 and Week 8.
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Change in Visual Analogue Scale for Mental Fatigue (VAS-MF)
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
VAS-MF is a single-item 0-100 mm visual analogue scale measuring perceived mental fatigue. Higher values indicate greater fatigue. This outcome assesses change in VAS-MF score from baseline to Week 4 and Week 8
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Change in PROMIS Fatigue Score
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
The PROMIS Fatigue Short Form assesses self-reported fatigue and its interference with daily functioning. Scores are reported as standardized T-scores (mean 50, SD 10); higher scores indicate greater fatigue. This outcome measures change in PROMIS Fatigue from baseline to Week 4 and Week 8.
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Change in Neuro-QoL Fatigue
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
Neuro-QoL Fatigue evaluates the impact of fatigue on quality of life in neurological conditions. Scores are converted to T-scores (mean 50, SD 10), with higher scores indicating worse fatigue-related QoL. This outcome measures change in Neuro-QoL Fatigue from baseline to Week 4 and Week 8
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Change in Symbol Digit Modalities Test (SDMT)
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
The SDMT is a widely used measure of information processing speed. The score reflects the number of correct symbol-digit matches completed in 90 seconds, with higher scores indicating better cognitive performance. This outcome assesses change in SDMT score from baseline to Week 4 and Week 8.
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Rate of Change in Daily Fatigue Severity (DFS) During the Treatment Period
Time Frame: Baseline through End of treatment (week 4)
Daily Fatigue Severity (DFS) is assessed using a repeated self-reported rating of fatigue severity. Participants respond to the question "How fatigued do you feel today?" using a 7-point Likert scale, where higher scores indicate greater fatigue. This outcome assesses the rate of change in DFS across the treatment period to characterize longitudinal changes in daily fatigue.
Baseline through End of treatment (week 4)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in MFIS Subscale Scores (Physical, Cognitive, Psychosocial)
Time Frame: Baseline to End of Treatment (week 4) and Follow-up (week 8)
The MFIS yields three subscale scores assessing physical, cognitive, and psychosocial fatigue impact. Higher scores indicate greater impairment. This outcome measures change in each subscale from baseline to Week 4 and Week 8.
Baseline to End of Treatment (week 4) and Follow-up (week 8)
Cognitive Performance During Stimulation (Embedded Virtual Reality Tasks)
Time Frame: Baseline through End of Treatment (week 4)
Cognitive performance is assessed using tasks embedded within the virtual reality environment during stimulation sessions. These tasks are designed to probe attention, processing speed, and learning dynamics while participants receive either active or sham stimulation. Performance data collected across sessions will be used for exploratory analyses of cognitive performance and learning trajectories during the treatment period.
Baseline through End of Treatment (week 4)
Treatment Acceptability Ratings
Time Frame: Week 2, Week 4, and Week 8
Longitudinal acceptability is evaluated at Weeks 2, 4 and 8 by asking participants about their willingness to use the device at home as a future treatment for MS-related fatigue. Responses provide insight into perceived usability, tolerability, and overall acceptability of the intervention over time.
Week 2, Week 4, and Week 8
Incidence of Adverse Events (AEs)
Time Frame: Baseline through Follow-up (week 8)
AEs are defined as any unfavorable medical occurrence during the study, whether or not considered related to the intervention. Events are categorized by severity and relationship to study treatment. This outcome measures the proportion of participants experiencing at least one AE.
Baseline through Follow-up (week 8)
Incidence of Serious Adverse Events (SAEs)
Time Frame: Baseline through Week 8
SAEs include events resulting in hospitalization, persistent disability, life-threatening conditions, or death. This outcome reports the number and proportion of participants experiencing SAEs during the study.
Baseline through Week 8
Tolerability: Session Attendance / Adherence Rate
Time Frame: Weeks 0-4
Tolerability is assessed through adherence to the prescribed stimulation schedule. This outcome measures the percentage of completed sessions out of the total required (16 sessions delivered over 4 weeks).
Weeks 0-4
Study Retention Rate
Time Frame: Baseline through Follow-up (week 8)
Retention rate is defined as the proportion of participants who complete the follow-up assessment (week 8) relative to those enrolled.
Baseline through Follow-up (week 8)
Events of Clinical Interest (Agitation/Confusion)
Time Frame: Immediately monitored following stimulation; Through Week 4
Events of clinical interest include agitation, confusion, or disorientation occurring within 1 hour of stimulation. This outcome captures their incidence and severity.
Immediately monitored following stimulation; Through Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clarity Health Technologies, Inc

Collaborators

Parc de Salut Mar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

December 16, 2025

First Submitted That Met QC Criteria

December 16, 2025

First Posted (Actual)

December 30, 2025

Study Record Updates

Last Update Posted (Actual)

February 3, 2026

Last Update Submitted That Met QC Criteria

January 30, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHT0002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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