Chronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy

NCT05655195 | Recruiting DMC FDA Device

• 1 other identifier: 2206000685
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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 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.

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

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  Immediately after blood draw at baseline and month 6 visits

Secondary Outcomes (3)

• Changes in the microbiome as measured by fecal samples

  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

  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

  Immediately after actigraph data download at baseline, month 3, and month 6

Study Arms (2)

Alzheimer's Active Arm

ACTIVE COMPARATOR

Exposure to active sensory stimulation (40Hz) for 60 minutes daily for the length of the trial (6 months).

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).

Device: GENUS device (sham settings)

Interventions

GENUS device (Active Settings) DEVICE

Participants in the active, experimental group will use the GENUS devices configured to active (40Hz) setting for 60 minutes daily for 6 months.

Also known as: Gamma Frequency Stimulation, Light and Sound Stimulation

Alzheimer's Active Arm

GENUS device (sham settings) DEVICE

Participants in the control group will use the GENUS devices configured to the sham settings for 60 minutes daily for 6 months.

Also known as: Gamma Frequency Stimulation, Light and Sound Stimulation

Alzheimer's Control Arm

Eligibility Criteria

• Age: 65 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Massachusetts Institute of Technology: lead

Study Sites (1)

Massachusetts Institute of Technology

Cambridge, Massachusetts, 02142, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Ultraviolet Therapy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phototherapy; Therapeutics

Study Officials

• Li Huei Tsai, PhD

  Massachusetts Institute of Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

gamma wave

CONTACT

617-258-7723; gamma.wave@mit.edu

Ana Trisini Lipsanopoulos, BS

CONTACT

617-258-7723; anat13@mit.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2022
• First Posted: December 19, 2022
• Study Start: December 14, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)