NCT05655195 · Massachusetts Institute of Technology
Chronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy
What this study is about
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.
View original scientific 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. 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.
Interventions
DEVICE
GENUS device (Active Settings)
Participants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 60 minutes daily for 6 months.
DEVICE
GENUS device (sham settings)
Participants in the control group will use the GENUS devices configured to the sham settings for 60 minutes daily for 6 months.
Primary outcome measures
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).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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
- 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.
Where
- Cambridge, Massachusetts
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 30, 2026 · Source of record for eligibility and locations