The GENUS (Gamma ENtrainment for US) trial is a Phase 2 clinical trial conducted by Massachusetts Institute of Technology (MIT) investigating whether non-invasive 40Hz gamma-frequency sensory stimulation can prevent cognitive decline in cognitively normal adults at risk for Alzheimer's Disease. Unlike transcranial electrical stimulation approaches, GENUS uses light, sound, and tactile devices to deliver sensory stimulation at the gamma frequency.
Study Details
| Parameter | Value | |-----------|-------| | NCT Number | [NCT07496918](https://clinicaltrials.gov/study/NCT07496918) | | Status | Recruiting | | Sponsor | Massachusetts Institute of Technology (MIT) | | Phase | Phase 2 | | Study Type | Interventional | | Design | Sequential, Single-arm feasibility | | Enrollment | 150 participants (estimated) | | Start Date | February 20, 2018 | | Estimated Completion | January 30, 2027 | | Location | MIT, Cambridge, Massachusetts, USA | | Acronym | GENUS (Gamma ENtrainment for US) |
Study Design
Approach
The GENUS trial employs a sequential design to evaluate feasibility and biological effects of 40Hz sensory stimulation:
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Gamma Frequency Sensory Stimulation — MIT GENUS Trial (NCT07496918)
Overview
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The GENUS (Gamma ENtrainment for US) trial is a Phase 2 clinical trial conducted by Massachusetts Institute of Technology (MIT) investigating whether non-invasive 40Hz gamma-frequency sensory stimulation can prevent cognitive decline in cognitively normal adults at risk for Alzheimer's Disease. Unlike transcranial electrical stimulation approaches, GENUS uses light, sound, and tactile devices to deliver sensory stimulation at the gamma frequency.
Study Details
| Parameter | Value | |-----------|-------| | NCT Number | [NCT07496918](https://clinicaltrials.gov/study/NCT07496918) | | Status | Recruiting | | Sponsor | Massachusetts Institute of Technology (MIT) | | Phase | Phase 2 | | Study Type | Interventional | | Design | Sequential, Single-arm feasibility | | Enrollment | 150 participants (estimated) | | Start Date | February 20, 2018 | | Estimated Completion | January 30, 2027 | | Location | MIT, Cambridge, Massachusetts, USA | | Acronym | GENUS (Gamma ENtrainment for US) |
Study Design
Approach
The GENUS trial employs a sequential design to evaluate feasibility and biological effects of 40Hz sensory stimulation:
Active Stimulation Group — 40Hz sensory stimulation using:
Visual: LED light devices delivering 40Hz flickering light
The GENUS approach is based on the hypothesis that gamma oscillations (30-100 Hz) are disrupted early in Alzheimer's disease, and that non-invasive sensory-driven gamma entrainment can restore normal neural function and potentially reduce pathological protein accumulation.
Key hypotheses being tested:
Neural entrainment: Can 40Hz sensory stimulation entrain endogenous gamma oscillations in the brain?
Safety: Is sensory gamma stimulation safe in cognitively normal adults?
Connectivity: Does gamma stimulation affect brain connectivity patterns?
Cognition: Does gamma stimulation improve neuropsychological measures?
Biomarkers: Does gamma stimulation affect blood biomarkers and gut microbiome?
Evidence from Preclinical Studies
Prior research supports the gamma entrainment approach:
Amyloid reduction: 40Hz sensory stimulation reduced amyloid-beta plaques in AD mouse models[@mart2024]
Cognitive improvement: Gamma-entrained mice showed improved performance on memory tasks
Microglial activation: Enhanced clearance of pathological proteins by microglia
Neuroprotection: Neuronal preservation in gamma-stimulated animals
A pilot study in patients with mild probable AD demonstrated feasibility and preliminary efficacy[@chan2022].
Intervention: GENUS Devices
Light Stimulation Device
The device uses light-emitting diodes (LEDs) to deliver visual gamma stimulation:
Configuration: Centrally-mounted tablet or phone displaying gamma-flickering content
Active device: Delivers light at 40Hz flicker rate
Sound Stimulation Device
Audio delivery through speakers:
Format: Videos with synchronized 40Hz audio tones
Purpose: Entertainment content during stimulation sessions
Tactile Stimulation Device
Wrist or hand-held device:
Mechanism: Vibrates or generates tactile stimulation at specific frequencies
Form factor: Worn on wrist or held in hand
Outcome Measures
Primary Outcomes
Effects of GENUS on brain oscillations (EEG)
Determine whether GENUS affects brain oscillations including gamma band
Timeframe: 1 year
Effects of GENUS on brain oscillations (MEG)
Magnetoencephalography measures of gamma activity
Timeframe: 1 year
Effects of GENUS on brain oscillations (MRI)
MRI-based measures of neural activity
Timeframe: 1 year
Secondary Outcomes
Microbiome evaluation
Fecal sample analysis using QIAamp PowerFecal Pro DNA Kit
DADA2 pipeline for microbial composition analysis
Principal component analyses and statistical comparisons
Blood biomarkers
Evaluation of blood-based biomarkers after 1-hour stimulation
Brain connectivity (EEG, MEG, MRI)
Resting-state connectivity measures
Gamma oscillation network analysis
Neuropsychiatric measures
Cognitive testing battery
Mood assessment
Eligibility Criteria
Inclusion Criteria
Adequate visual and auditory acuity for stimulation participation
Ability to comply with neuropsychological testing and study procedures
Cognitively normal, healthy adults
Exclusion Criteria
History of seizure or epilepsy diagnosis
MRI contraindications:
Pacemakers
Aneurysm clips
Artificial heart valves
Ear implants
Metal fragments or foreign objects in eyes, skin, or body
3. Investigator discretion regarding ability to complete key procedures
Demographics
Age: 18-100 years
Sex: All
Healthy volunteers: Yes
Mechanism of Action
Gamma Oscillation Foundation
Information processing in the brain occurs through synchronized neuronal activity in the form of network oscillations. Gamma-band oscillation (30-100 Hz) is critical for:
Attention: Gamma synchronizes neural populations for sensory integration
Memory formation: Hippocampal gamma coordinates information transfer during encoding
[Chan D, Suk HJ, Jackson BL, et al., Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies. PLoS One. 2022 Dec 1;17(12):e0278412 (PMID:36454969)](https://pubmed.ncbi.nlm.nih.gov/36454969/)
[Gamma Frequency Sensory Stimulation (NCT07496918) — MIT GENUS](http://scidex.ai/artifact/wiki-clinical-trials-gamma-frequency-sensory-stimulation-mit-nct07496918)