Alzheimer DiseaseNCT05776641
Gamma Light and Sound Stimulation to Prevent Dementia in Cognitively Normal People at Risk for Alzheimer's Disease
A study testing GENUS in people with Alzheimer Disease and Family Members, run by Massachusetts General Hospital at 2 sites 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. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. Read more about this study
- Who is it for?
- Ages 55 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Family Members
- What is being tested?
- GENUS
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Jun 2024to May 2027
- 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 55 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Between 55 - 90 years of age, inclusive.
- Immediate family history of Alzheimer's disease.
- Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
- Clinical Dementia Rating Global Score of 0 at baseline.
- Delayed Recall score on the Logical Memory IIa subtest of 8 to 15 at baseline or expected score range for cognitively normal adjusted for education level.
- Low serum amyloid levels at baseline.
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- Elevated fibrillar amyloid using 11C PiB PET at baseline between 20 - 70 CL.
- Willing and able to undergo MRI brain and PET brain scans.
- Adequate visual and auditory acuity to allow for neuropsychological testing.
- Able to comply with neuropsychological testing and other study procedures in opinion of site PI.
- Willing and able to complete baseline assessments, and willing to participate in 13-month study protocol.
- Willing to provide blood samples at specified timepoints. Willing to consider contributing CSF samples at specified timepoints, if asked.
Who cannot join
- MRI contraindications, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body.
- High myopia < -7 diopters, or untreated cataracts that affect vision.
- Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
- For subjects agreeing to undergo lumbar punctures, history of bleeding disorders or laboratory results indicating low platelet levels are exclusionary for the procedure.
- Concomitant medications:
- Treatment with NMDA antagonists.
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- For subjects undergoing lumbar puncture, current use of warfarin or similar anti-coagulants is exclusionary for the procedure.
- Clinical conditions:
- History of seizure or medical diagnosis of epilepsy.
- Female subjects who are pregnant or currently breastfeeding.
- History of severe allergic or anaphylactic reactions.
- Longstanding premorbid history (i.e., longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed.
- Neurodegenerative disorder associated with cognitive impairment.
- Renal disease.
- MR imaging findings such as stroke, tumor, leukoencephalopathy that could preclude meaningful analyses of clinical and imaging data in the opinion of the site PI, such as:
- Severe leukoencephalopathy seen on MRI.
- Relevant structural abnormality (i.e., normal pressure or obstructive hydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).
- Cerebral amyloid angiopathy, evidenced by T2* or other susceptibility weighted-MRI.
- Laboratory findings, if known (study does not perform testing) suggestive of systemic illness such as renal disease.
- Site investigator's discretion, if s/he feels the subject cannot complete sufficient key study procedures. Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the Project Director.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
MJ Quay, MS, 617-807-0856, gamma.wave@mit.edu
Andrew Becker, BS, 617-258-7723, gamma.wave@mit.edu
- Recruiting
Massachusetts Institute of Technology
Cambridge, Massachusetts, 02139
About this study
Official title: Prevention of Alzheimer's Disease Using Gamma Entrainment
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 Tsai 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. A light and sound device was developed for humans that stimulates the brain at 40Hz that can be used safely at home. The goal of this study is to see if using this device can prevent dementia in people who are at risk for developing Alzheimer's disease.
Read the detailed description
The investigators are recruiting participants aged 55+ with normal memory who have or had a close family member with Alzheimer's disease. 200 participants will undergo a blood test and a subset will undergo an amyloid PET scan and only 50 participants who have cerebral amyloid deposits will continue in the study. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for 12 months at home, for 60 minutes each day when they are awake. Participants will come to the Massachusetts General Hospital in Boston for 4-6 visits: before starting the stimulation, at 6 months, and after 12 months of usage. The participants will undergo PET scans, MRI, EEG, blood tests and memory tests and questionnaires at each visit to monitor progress. In addition, people may elect to allow for us to study their cerebral spinal fluid. Participants will also wear a "fitbit" like watch to monitor sleep and activity throughout the study. The goal of this study is to evaluate whether stimulation with our device at 40Hz will reduce AD pathology in the brain.
- Conditions
- Alzheimer Disease, Family Members
- Being tested
- GENUS
- Keywords
- Cognitively normal, Alzheimer's disease, Gamma, Amyloid
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GENUSDevice
Participants will use the GENUS light and sound device at home for 60 minutes daily for 12 months
| Study group | Role | What they receive |
|---|---|---|
| Active GENUS light and sound | Active comparator | The device is a light and sound device that delivers light stimulation using light-emitting diodes (LED) and sound stimulation through a speaker, with a centrally-mounted tablet that plays videos for entertainment. The device will be positioned on an easel such that the tablet is eye level with the participant while they are sitting 5 feet away. The active device delivers light and sound at 40Hz rate. Receives: Device: GENUS |
| Sham GENUS light and sound | Sham comparator | The device is the same as the active device but it delivers light and sound at different frequencies. Receives: Device: GENUS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in brain amyloid deposition over the study period, as measured by PiB PET.
The investigators will evaluate changes from baseline in amyloid deposition by using Pittsburgh compound B (PiB) PET, which is a standard for AD trial biomarkers, to assess progression towards AD with active or sham treatment.
Measured: Baseline to 12 months
Secondary outcomes (8)
Changes in brain tau deposition
The investigators will evaluate changes from baseline in tau deposition by using MK-6240 PET
Measured: Baseline to 12 months
Changes in brain structure using structural MRI
The investigators will evaluate changes in brain structure using structural MRI. Preliminary data show prevention of brain atrophy after 3 months of GENUS as measured by ventricular dilation and hippocampal volume. Using structural MRI, the investigators will evaluate brain volume, cortical thickness and ventricular volume.
Measured: Baseline to 12 months
Changes in brain electrical activity
The investigators will evaluate brain electrical activity using longitudinal EEG (ie, gamma band power)
Measured: Baseline to 12 months
Changes in brain connectivity by functional MRI
The investigators will evaluate connectivity using resting state functional MRI to assess changes in brain networks (ie, default mode network).
Measured: Baseline to 12 months
Changes to rest-activity parameters using actigraphy.
Actigraphy will be used to evaluate rest-activity parameters (ie, interdaily stability
Measured: Baseline to 12 months
Changes in blood biomarkers of AD
Changes in Alzheimer's blood-based biomarkers (e.g. plasma Aβ42/Aβ40 ratio, Aβ42, Aβ40, p-tau, and neurofilament light) assessed by longitudinal blood sample collection
Measured: Baseline to 12 months
Compliance of usage as measured by timestamp tracking and eye-tracking technology
The device contains both a time-counter to track 'on time' and a camera that records images for eye-tracking, to quantitatively determine compliance with looking directly at the device. This method also quantifies whether the subjects are awake for the duration of treatment. Previous work with healthy older adults and a small cohort of mild AD patients have had 90% compliance.
Measured: Baseline to 12 months
Change from baseline in CSF levels of amyloid and tau.
Lumbar puncture and CSF collection will be optional for participants, but will be informative as to the investigator's hypothesized mechanisms of clearance.
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2023
- Study start21 Jun 2024
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (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.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts Institute of Technology
- Responsible party
- Principal investigator, Diane Chan, Massachusetts General Hospital
- Investigators
- Diane Chan, MD PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05776641
- Sponsor's protocol ID
- 2021P002885
- Status last verified
- Jun 2026
- First submitted
- 29 Nov 2022
- Last updated
- 18 Jun 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 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Alzheimer's Disease Using Gamma Entrainment
- ClinicalTrials.gov ID
- NCT05776641
- Acronym / sponsor ID
- 2021P002885
- Conditions
- Alzheimer Disease, Family Members
- Keywords
- Cognitively normal, Alzheimer's disease, Gamma, Amyloid
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Massachusetts Institute of Technology
- Study start
- 21 Jun 2024 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 20 Mar 2023 (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. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The Tsai 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. A light and sound device was developed for humans that stimulates the brain at 40Hz that can be used safely at home. The goal of this study is to see if using this device can prevent dementia in people who are at risk for developing Alzheimer's disease.
Detailed description
The investigators are recruiting participants aged 55+ with normal memory who have or had a close family member with Alzheimer's disease. 200 participants will undergo a blood test and a subset will undergo an amyloid PET scan and only 50 participants who have cerebral amyloid deposits will continue in the study. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for 12 months at home, for 60 minutes each day when they are awake. Participants will come to the Massachusetts General Hospital in Boston for 4-6 visits: before starting the stimulation, at 6 months, and after 12 months of usage. The participants will undergo PET scans, MRI, EEG, blood tests and memory tests and questionnaires at each visit to monitor progress. In addition, people may elect to allow for us to study their cerebral spinal fluid. Participants will also wear a "fitbit" like watch to monitor sleep and activity throughout the study. The goal of this study is to evaluate whether stimulation with our device at 40Hz will reduce AD pathology in the brain.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active GENUS light and sound | Active comparator | Device: GENUSThe device is a light and sound device that delivers light stimulation using light-emitting diodes (LED) and sound stimulation through a speaker, with a centrally-mounted tablet that plays videos for entertainment. The device will be positioned on an easel such that the tablet is eye level with the participant while they are sitting 5 feet away. The active device delivers light and sound at 40Hz rate. |
| Sham GENUS light and sound | Sham comparator | Device: GENUSThe device is the same as the active device but it delivers light and sound at different frequencies. |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Between 55 - 90 years of age, inclusive.
- Immediate family history of Alzheimer's disease.
- Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
- Clinical Dementia Rating Global Score of 0 at baseline.
- Delayed Recall score on the Logical Memory IIa subtest of 8 to 15 at baseline or expected score range for cognitively normal adjusted for education level.
Key exclusion criteria (20 listed)
- MRI contraindications, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body.
- High myopia < -7 diopters, or untreated cataracts that affect vision.
- Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
- For subjects agreeing to undergo lumbar punctures, history of bleeding disorders or laboratory results indicating low platelet levels are exclusionary for the procedure.
- Concomitant medications:
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 |
|---|---|---|
| GENUSParticipants will use the GENUS light and sound device at home for 60 minutes daily for 12 months | Device | Active GENUS light and sound, Sham GENUS light and sound |
Primary outcome
Changes in brain amyloid deposition over the study period, as measured by PiB PET.
Time frame: Baseline to 12 months
The investigators will evaluate changes from baseline in amyloid deposition by using Pittsburgh compound B (PiB) PET, which is a standard for AD trial biomarkers, to assess progression towards AD with active or sham treatment.
8 secondary outcomes
Changes in brain tau deposition
Time frame: Baseline to 12 months
Changes in brain structure using structural MRI
Time frame: Baseline to 12 months
Changes in brain electrical activity
Time frame: Baseline to 12 months
Changes in brain connectivity by functional MRI
Time frame: Baseline to 12 months
Changes to rest-activity parameters using actigraphy.
Time frame: Baseline to 12 months
Changes in blood biomarkers of AD
Time frame: Baseline to 12 months
Compliance of usage as measured by timestamp tracking and eye-tracking technology
Time frame: Baseline to 12 months
Change from baseline in CSF levels of amyloid and tau.
Time frame: Baseline to 12 months
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 18 Jun 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.
Diane Chan, MD PhD principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GENUS in people with Alzheimer Disease and Family Members, run by Massachusetts General Hospital at 2 sites 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 12 inclusion and 20 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 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Angelina Singavarapu, BS (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?
Changes in brain amyloid deposition over the study period, as measured by PiB PET. (time frame: Baseline to 12 months). 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 18 Jun 2026.