Alzheimer DiseaseNCT05655195
Chronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy
A study testing GENUS device (Active Settings) in people with Alzheimer Disease and Alzheimer Disease, Early Onset, run by Massachusetts Institute of Technology at 1 site in United States.
Trial summary
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and… Read more about this study
- Who is it for?
- Ages 65 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Alzheimer Disease, Early Onset, Alzheimer Disease, Late Onset
- What is being tested?
- GENUS device (Active Settings)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 2022to 1 Sep 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 100 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Subjects may be enrolled into the study if they meet all of the following criteria:
- Subject is between the ages of 65 - 100.
- Subject must have mild Alzheimer's disease with a Mini Mental State Exam (MMSE) score of 19-26.
- Subject is willing to sign informed consent document.
- If subject is deemed to not have capacity to sign the informed consent, he/she will need a legally authorized representative to provide surrogate consent.
- Able to complete the 1st month of at home stimulation at their primary residence. If subjects plan to spend more than 1 week away from their primary residence during the trial, their inclusion must be assessed by the research team.
Who cannot join
- Subjects who meet any of the following conditions will not be enrolled in the study:
- Subjects who do not have healthcare.
- Subjects who are currently taking amyloid reducing therapy.
- Subjects who have > 4 cerebral microbleeds or 1 macrobleed in their brain
- Active treatment on a dosage of one or more psychiatric agents (e.g. antidepressants, antipsychotics, etc) for LESS THAN three months (a stable dose for greater than or equal to three months is ok).
- Subjects who are actively diagnosed with cancer and undergoing cancer-related treatments
Show all 21Show fewer
- Subjects who are being treated with N-methyl-D-aspartate (NMDA) receptor antagonists (eg. Memantine).
- Subjects on medications that lower seizure threshold such as wellbutrin, ciprofloxacin, levofloxacin, etc.
- Subjects with history of seizure or epilepsy
- Subjects with clinically significant suicide risk and/or suicide attempt in the past 1 year.
- Subjects with behavioral problems such as aggression/agitation/impulsivity that might interfere with their ability to comply with protocol.
- Subjects with untreated or unstable depression
- Active treatment with one or more anti-epileptic agent.
- Subjects who have had a stroke within the past 24 months.
- Subjects who have had eye surgery in the last 3 months or are scheduled to have eye surgery in the next 6 months (during the study)
- Subjects diagnosed with migraine headache.
- Subjects who have an active implantable medical device including but not limited to implantable cardioverter defibrillator (ICD), deep brain stimulator (DBS), cardiac pacemaker, and/or sacral nerve stimulator.
- Subjects who have profound hearing or visual impairment.
- Subjects who have a life expectancy of less than 2 years.
- Subjects who are pregnant.
- Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke, progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts Institute of Technology
Cambridge, Massachusetts, 02142
Ana Trisini Lipsanopoulos, BS, 617-258-7723, anat13@mit.edu
About this study
Official title: Chronic Treatment of Alzheimer's Disease With Gamma Frequency Stimulation
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for at least one year and completing yearly study visits. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.
Read the detailed description
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. The investigators also developed a vibrating device for humans that stimulates the brain at 40Hz via tactile stimulation. The investigators want to see if using these devices can prevent dementia in people who are at risk for developing Alzheimer's disease.
The investigators are recruiting 60 participants who have been diagnosed with Alzheimer's disease to participate in this study. There will be a small cohort of 4 early-onset AD participants aged 50-65, and the rest will be diagnosed with typical AD and aged 65+. It will take place at the Massachusetts Institute of Technology in Cambridge, MA, and will last 6 months with 3 required visits to the institution: the first at baseline, the second at three months, and the last after six months. Visits will include blood tests, fecal samples, EEG (using light, sound, and tactile stimulation), MRI, memory and cognitive tests, and questionnaires to monitor progress. Participants will take home a gamma light and sound device to use daily as well as a "Fitbit" type of watch to wear to track sleep patterns. Half of the participants will receive sham treatment, meaning they will use the investigators' device but the light and sound will not be set at 40Hz. The other half will receive the same device but it will be set to stimulate the brain with 40Hz light and sound. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for six months at home, for 60 minutes each day when they are awake. After six months, participants will have the option of continuing in the study for at least one year, during which time they will be guaranteed the 40Hz active treatment, regardless of their original group assignment. During this time, participants will continue to use the device for 60 minutes every day, and they will come in for visits to MIT at yearly time points.
The purpose of this study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation is possible in those with AD, and whether functional connectivity in their brain and molecular biomarkers of AD will change after 6 months of daily treatment with the investigators' light and sound device. The treatment's impact on the microbiome, cognition, and daily sleep and activity will also be measured. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.
- Conditions
- Alzheimer Disease, Alzheimer Disease, Early Onset, Alzheimer Disease, Late Onset, Alzheimer's Disease (Incl Subtypes), Alzheimer's, Alzheimer's Disease
- Being tested
- GENUS device (Active Settings), GENUS device (sham settings)
- Keywords
- Alzheimer's, Alzheimer, Alzheimer's disease, Light and Sound Stimulation, Tactile Stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GENUS device (Active Settings)Device
Also called Gamma Frequency Stimulation, Light and Sound Stimulation
Participants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 60 minutes daily for 6 months.
GENUS device (sham settings)Device
Also called Gamma Frequency Stimulation, Light and Sound Stimulation
Participants in the control group will use the GENUS devices configured to the sham settings for 60 minutes daily for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's Active Arm | Active comparator | Exposure to active sensory stimulation (40Hz) for 60 minutes daily for the length of the trial (6 months). Receives: Device: GENUS device (Active Settings) |
| Alzheimer's Control Arm | Sham comparator | Exposure to control stimulation (sham) for 60 minutes daily for the length of the trial (6 months). Receives: Device: GENUS device (sham settings) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of gamma frequency stimulation as assessed by a change of gamma frequency waves during EEG
Feasibility of gamma frequency stimulation in subjects with AD will be assessed by analyzing the EEG data from each subject as they undergo gamma light, sound, and tactile stimulation. Investigators will look for a sign of change in gamma frequency waves and determine the percent of subjects who show this change. This change will be assessed through FFT analyses on the EEG data in MATLAB, which looks at the different frequencies that were present during the EEG session.
Measured: Immediately after completing the stimulation at baseline, month 3, and month 6 visits
Baseline incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Measured: Immediately after the completion of the stimulation at baseline.
Mid-point incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Measured: Immediately after the completion of the stimulation at Month 3.
Endpoint incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Measured: Immediately after the completion of the stimulation at the end of the trial- Month 6 timepoints.
Change in stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Measured: During weekly phone calls throughout the 6-month trial period
Changes in functional brain connectivity as measured by changes in brain white matter on functional MRI scans
Exploratory measure to check if there are changes in functional brain connectivity after 6 months of daily treatment with the light and sound device. Diffusion tensor imaging (DTI) will be used to test the connectivity and blood flow of the brain by identifying major white matter tracts. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Measured: At baseline, month 3, and month 6 visits during MRI sessions
Changes in functional brain connectivity as measured by changes in blood-oxygen-level-dependent (BOLD) signals on functional MRI scans
Exploratory measure to check if there are changes in functional brain connectivity after 6 months of daily treatment with the light and sound device. BOLD (blood-oxygen-level-dependent) imaging will be used to determine how regions are communicating and activating together via blood flow. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Measured: At baseline, month 3, and month 6 visits during MRI sessions
Changes in gamma entrainment, as measured by the change in response to 40Hz frequency during EEG sessions
Exploratory measure to check if there are changes in gamma entrainment after months of daily treatment with the light and sound device. Gamma entrainment during light and sound stimulation will also be assessed using EEG and FFT analyses in MATLAB to determine the degree to which the brain is responding to the 40hz frequency. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Measured: At baseline, month 3, and month 6 visits during EEG sessions
Changes in molecular biomarkers in AD as measured by RNA sequencing data, particularly those related to inflammation and amyloid levels
Exploratory measure to check if there are changes in molecular biomarkers of AD (based on RNA sequencing data) as a result of 6 months of daily treatment with the light and sound device. RNA information will be extracted from subjects' blood samples at the baseline and month 6 visits. RNA sequencing of this blood is included based on previous transcriptomic analysis of peripheral leukocytes that showed that inflammation-related genes are related to neurodegenerative disease such as AD. Change will be determined by comparing RNA sequencing data between baseline and month 6 (the beginning and end of the trial).
Measured: Immediately after blood draw at baseline and month 6 visits
Secondary outcomes (3)
Changes in the microbiome as measured by fecal samples
At baseline and month 6, subjects will produce a fecal sample and hand it off to study staff for storage and sample processing using the QIAamp PowerFecal Pro DNA Kit (Qiagen). Data will then be analyzed using the Divisive Amplicon Denoising Algorithm 2 (DADA2) pipeline, which will provide gut microbial composition in the different experimental groups. Pipeline outputs involve principal component analyses, and a custom in-house script will be used to make statistical comparisons. Change will be assessed by comparing the fecal sample analyses between baseline and month 6.
Measured: Immediately after fecal sample collection at baseline and month 6
Changes in cognitive performance as assessed by scores on an Alzheimer's cognitive testing battery
Exploratory measure to check if there is any change in cognitive performance as a result of 6 months of daily sessions with the light and sound device. Alzheimer's testing battery will be administered at baseline, month 3, and month 6 visits, and change will be determined by comparing cognitive performance (via standardized scores) at these three timepoints. These tests measure a variety of cognitive abilities, including attention, different types of memory, processing speed, visual acuity, and more.
Measured: Immediately after completion of cognitive batteries at baseline, month 3, and month 6 Visits
Changes in sleep/wake patterns, as measured by actigraph watch analyses
Subjects will be expected to wear a GTX9 actigraph watch daily to record activity and sleep/wake patterns throughout the 6-months of the trial. This watch is like a regular wrist watch, but it records daily activity and patterns through light and movement. The subject will be given their watch ~2 weeks before the trial start-date, and they will bring it in with them at baseline, month 3, and month 6 visits so researchers can download their data to analyze their length and quality of sleep, as well as their other circadian rhythms and patterns throughout each day. Change will be assessed by comparing actigraph data between baseline, month 3, and month 6, as subject progress throughout the trial.
Measured: Immediately after actigraph data download at baseline, month 3, and month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2022
- Study start14 Dec 2022
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts Institute of Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Li Huei Tsai, PhD, Principal investigator, Massachusetts Institute of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05655195
- Sponsor's protocol ID
- 2206000685
- Status last verified
- Mar 2026
- First submitted
- 19 Oct 2022
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronic Treatment of Alzheimer's Disease With Gamma Frequency Stimulation
- ClinicalTrials.gov ID
- NCT05655195
- Acronym / sponsor ID
- 2206000685
- Conditions
- Alzheimer Disease, Alzheimer Disease, Early Onset, Alzheimer Disease, Late Onset, Alzheimer's Disease (Incl Subtypes), Alzheimer's, Alzheimer's Disease
- Keywords
- Alzheimer's, Alzheimer, Alzheimer's disease, Light and Sound Stimulation, Tactile Stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Massachusetts Institute of TechnologyUniversity, hospital or other
- Study start
- 14 Dec 2022 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 19 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for at least one year and completing yearly study visits. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.
Detailed description
Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The investigator's lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. The investigators also developed a vibrating device for humans that stimulates the brain at 40Hz via tactile stimulation. The investigators want to see if using these devices can prevent dementia in people who are at risk for developing Alzheimer's disease.
The investigators are recruiting 60 participants who have been diagnosed with Alzheimer's disease to participate in this study. There will be a small cohort of 4 early-onset AD participants aged 50-65, and the rest will be diagnosed with typical AD and aged 65+. It will take place at the Massachusetts Institute of Technology in Cambridge, MA, and will last 6 months with 3 required visits to the institution: the first at baseline, the second at three months, and the last after six months. Visits will include blood tests, fecal samples, EEG (using light, sound, and tactile stimulation), MRI, memory and cognitive tests, and questionnaires to monitor progress. Participants will take home a gamma light and sound device to use daily as well as a "Fitbit" type of watch to wear to track sleep patterns. Half of the participants will receive sham treatment, meaning they will use the investigators' device but the light and sound will not be set at 40Hz. The other half will receive the same device but it will be set to stimulate the brain with 40Hz light and sound. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for six months at home, for 60 minutes each day when they are awake. After six months, participants will have the option of continuing in the study for at least one year, during which time they will be guaranteed the 40Hz active treatment, regardless of their original group assignment. During this time, participants will continue to use the device for 60 minutes every day, and they will come in for visits to MIT at yearly time points.
The purpose of this study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation is possible in those with AD, and whether functional connectivity in their brain and molecular biomarkers of AD will change after 6 months of daily treatment with the investigators' light and sound device. The treatment's impact on the microbiome, cognition, and daily sleep and activity will also be measured. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's Active Arm | Active comparator | Device: GENUS device (Active Settings)Exposure to active sensory stimulation (40Hz) for 60 minutes daily for the length of the trial (6 months). |
| Alzheimer's Control Arm | Sham comparator | Device: GENUS device (sham settings)Exposure to control stimulation (sham) for 60 minutes daily for the length of the trial (6 months). |
Who may qualify
- Ages
- 65 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- Subject is between the ages of 65 - 100.
- Subject must have mild Alzheimer's disease with a Mini Mental State Exam (MMSE) score of 19-26.
- Subject is willing to sign informed consent document.
- If subject is deemed to not have capacity to sign the informed consent, he/she will need a legally authorized representative to provide surrogate consent.
- Able to complete the 1st month of at home stimulation at their primary residence. If subjects plan to spend more than 1 week away from their primary residence during the trial, their inclusion must be assessed by the research team.
Key exclusion criteria (21 listed)
- Subjects who do not have healthcare.
- Subjects who are currently taking amyloid reducing therapy.
- Subjects who have > 4 cerebral microbleeds or 1 macrobleed in their brain
- Active treatment on a dosage of one or more psychiatric agents (e.g. antidepressants, antipsychotics, etc) for LESS THAN three months (a stable dose for greater than or equal to three months is ok).
- Subjects who are actively diagnosed with cancer and undergoing cancer-related treatments
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GENUS device (Active Settings)Also: Gamma Frequency Stimulation, Light and Sound StimulationParticipants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 60 minutes daily for 6 months. | Device | Alzheimer's Active Arm |
| GENUS device (sham settings)Also: Gamma Frequency Stimulation, Light and Sound StimulationParticipants in the control group will use the GENUS devices configured to the sham settings for 60 minutes daily for 6 months. | Device | Alzheimer's Control Arm |
Primary outcome
Feasibility of gamma frequency stimulation as assessed by a change of gamma frequency waves during EEG
Time frame: Immediately after completing the stimulation at baseline, month 3, and month 6 visits
Feasibility of gamma frequency stimulation in subjects with AD will be assessed by analyzing the EEG data from each subject as they undergo gamma light, sound, and tactile stimulation. Investigators will look for a sign of change in gamma frequency waves and determine the percent of subjects who show this change. This change will be assessed through FFT analyses on the EEG data in MATLAB, which looks at the different frequencies that were present during the EEG session.
Baseline incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Time frame: Immediately after the completion of the stimulation at baseline.
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Mid-point incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Time frame: Immediately after the completion of the stimulation at Month 3.
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Endpoint incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Time frame: Immediately after the completion of the stimulation at the end of the trial- Month 6 timepoints.
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Change in stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
Time frame: During weekly phone calls throughout the 6-month trial period
Tolerability and safety of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation and denoting any adverse effects. Subjects will be asked specifically about headaches, light headedness, nausea, dizziness, dry eye, eye strain, light sensitivity, ringing in ears, and any other symptoms they are experiencing.
Changes in functional brain connectivity as measured by changes in brain white matter on functional MRI scans
Time frame: At baseline, month 3, and month 6 visits during MRI sessions
Exploratory measure to check if there are changes in functional brain connectivity after 6 months of daily treatment with the light and sound device. Diffusion tensor imaging (DTI) will be used to test the connectivity and blood flow of the brain by identifying major white matter tracts. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Changes in functional brain connectivity as measured by changes in blood-oxygen-level-dependent (BOLD) signals on functional MRI scans
Time frame: At baseline, month 3, and month 6 visits during MRI sessions
Exploratory measure to check if there are changes in functional brain connectivity after 6 months of daily treatment with the light and sound device. BOLD (blood-oxygen-level-dependent) imaging will be used to determine how regions are communicating and activating together via blood flow. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Changes in gamma entrainment, as measured by the change in response to 40Hz frequency during EEG sessions
Time frame: At baseline, month 3, and month 6 visits during EEG sessions
Exploratory measure to check if there are changes in gamma entrainment after months of daily treatment with the light and sound device. Gamma entrainment during light and sound stimulation will also be assessed using EEG and FFT analyses in MATLAB to determine the degree to which the brain is responding to the 40hz frequency. This data will be collected at baseline, month 3, and month 6 for each subject, and change will be determined by comparing these timepoints.
Changes in molecular biomarkers in AD as measured by RNA sequencing data, particularly those related to inflammation and amyloid levels
Time frame: Immediately after blood draw at baseline and month 6 visits
Exploratory measure to check if there are changes in molecular biomarkers of AD (based on RNA sequencing data) as a result of 6 months of daily treatment with the light and sound device. RNA information will be extracted from subjects' blood samples at the baseline and month 6 visits. RNA sequencing of this blood is included based on previous transcriptomic analysis of peripheral leukocytes that showed that inflammation-related genes are related to neurodegenerative disease such as AD. Change will be determined by comparing RNA sequencing data between baseline and month 6 (the beginning and end of the trial).
3 secondary outcomes
Changes in the microbiome as measured by fecal samples
Time frame: Immediately after fecal sample collection at baseline and month 6
Changes in cognitive performance as assessed by scores on an Alzheimer's cognitive testing battery
Time frame: Immediately after completion of cognitive batteries at baseline, month 3, and month 6 Visits
Changes in sleep/wake patterns, as measured by actigraph watch analyses
Time frame: Immediately after actigraph data download at baseline, month 3, and month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Li Huei Tsai, PhD principal investigator
Massachusetts Institute of Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GENUS device (Active Settings) in people with Alzheimer Disease and Alzheimer Disease, Early Onset, run by Massachusetts Institute of Technology at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact gamma wave (617-258-7723, gamma.wave@mit.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of gamma frequency stimulation as assessed by a change of gamma frequency waves during EEG (time frame: Immediately after completing the stimulation at baseline, month 3, and month 6 visits). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.