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

Clarity Health Technologies

Status: Not yet enrolling

Conditions: Multiple Sclerosis

Treatments: Device: Virtual Reality Sham Sensory Stimulation; Device: Virtual Reality Gamma Sensory Stimulation

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07310862

CHT0002

Details and patient eligibility

About

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.

Full 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 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

30 participants in 2 patient groups

Gamma Sensory Stimulation

Active Comparator group

Description:

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.

Treatment:

Device: Virtual Reality Gamma Sensory Stimulation

Sham Sensory Stimulation

Sham Comparator group

Description:

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.

Treatment:

Device: Virtual Reality Sham Sensory Stimulation