Daily Light and Sound Stimulation to Improve Brain Functions in Alzheimer's Disease

Study Overview
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Brief Summary
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In this trial, the safety and effect of daily exposure to light and sound stimulation on people with mild Alzheimer's Disease (AD) will be studied. COVID-19 Amendment: Due to the ongoing suspension of all in-person humans subject research across MIT in response to the COVID-19 pandemic, all enrolled participants who have not completed their 6-month visit will have their visit postponed to 9 months with a follow up at 18 months. Subjects who have completed their 6-month visit will still be instructed to continue and return at Month 12 for an evaluation. OPTIONAL: If the subject would like to come in for an evaluation between Month 9 and 18, we will invite participants to come on Month 12 to complete cognitive testing and EEG.

Detailed Description
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After screening for eligibility, subjects will be randomized into one of two study groups in a 1:1 ratio. Each subject will use a non-invasive light and sound device, called the GENUS device, at home for 1 hour per day for 6 or 9 months. The GENUS device, which is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation, delivers light and sound at different frequencies. Subjects in the first group will use the device with active settings, and subjects in the second group will use the device with sham settings. After 6 or 9 months of the daily usage of the device, all subjects will be given an option to continue the daily usage for additional 6 or 9 months. For these additional 6 or 9 months, the device will be set to active settings for all subjects who choose to remain in the study. Over the first 6 or 9 months, cognitive, mental health and memory evaluations will be performed at baseline, after 1 month, after 3 months, and after 6 or 9 months of daily usage of the device. Blood draws as well as hearing and vision tests will be performed at baseline and after 6 or 9 months of daily usage of the device. Magnetic resonance imaging (MRI) and electroencephalogram (EEG) will also be performed at baseline, after 3 months, and after 6 or 9 months of daily usage of the device. For subjects who choose to continue the daily usage of the device for additional 6 or 9 months, MRI, EEG as well as cognitive, mental health and memory evaluations will be performed at the end of the 6 or 9 additional months of daily usage. One month after the completion of the daily usage, EEG as well as cognitive, mental health and memory evaluations will be performed (this will be 7 or 10 months after the start of the study for subjects who choose not to continue the daily usage of the device after the initial 6 or 9 months; this will be 13 or 19 months after the start of the study for subjects who choose to continue the daily usage of the device for additional 6 or 9 months after the initial 6 or 9 months). Participants who complete the study protocol and finish the final study visit at Month 12 or 19 will be offered a long-term extension for a total of 36 months with yearly follow up evaluations.

Official Title
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Chronic Treatment of Alzheimer's Disease With Gamma Frequency Stimulation

Conditions
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Alzheimer Disease, Alzheimer Dementia

Intervention / Treatment
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* Device: GENUS device (Active Settings)
* Device: GENUS device (Sham Settings)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is between the ages of 50 - 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. Subjects whose primary residence is within 2 hours of Boston 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 do not have healthcare. 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 within the past 24 months. Subjects with clinically significant suicide risk and/or suicide attempt in the past 12 months. Subjects with behavioral problems such as aggression/agitation/impulsivity that might interfere with their ability to comply with protocol. Active treatment with one or more anti-epileptic agent. Subjects who have had a stroke within the past 24 months. Subjects diagnosed with migraine headache. Active treatment with one or more psychiatric agent (e.g. antidepressants, antipsychotics, etc). 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 24 months. Subjects who are pregnant.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomly assigned to one of two study groups. Subjects in the first group will use the GENUS device with active settings for 6 or 9 months, and subjects in the second group will use the GENUS device with sham settings for 6 or 9 months. At the end of the 6 or 9 month period, all subjects will be given an option to continue the usage of the GENUS device for additional 6 or 9 months. For these additional 6 or 9 months, the device will be set to active settings for all subjects who choose to remain in the study. A 36-month compassionate use extension will be offered at the completion of all of the study visits.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily exposure to active stimulation<br>Subjects in this arm will receive daily exposure to active stimulation | Device: GENUS device (Active Settings)<br>* Participants in the experimental group will use the GENUS device configured to active settings for 60 minutes daily over 6 or 9 months. After 6 or 9 months, each participant will be given an option to continue the daily usage of the GENUS device configured to active settings for additional 6 or 9 months. Note: Due to the COVID-19 pandemic, participants who have not yet reached the 6-month mark will have their 6 month visit postponed to 9 months.<br>* Other names: Light and sound stimulation;|
| Sham Comparator: Daily exposure to control stimulation<br>Subjects in this arm will receive daily exposure to control stimulation | Device: GENUS device (Sham Settings)<br>* Participants in the control group will use the GENUS device configured to sham settings for 60 minutes daily over 6 or 9 months. After 6 or 9 months, each participant will be given an option to continue the daily usage of the GENUS device configured to active settings for additional 6 or 9 months. Note: Due to the COVID-19 pandemic, participants who have not yet reached the 6-month mark will have their 6 month visit postponed to 9 months.<br>* Other names: Light and sound stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of at-home light and sound stimulation: amount of time of device usage per day | Feasibility of daily at-home light and sound stimulation will be assessed by keeping track of the amount of time the GENUS device is used per day. The device will automatically log the start and end times of the device usage. The log data will be collected and assessed at the interim analysis time points (Month 1, Month 3) and later time points (Month 6 or 9 and Month 12 or 18). | Over 6 or 9 months (or over 12 or 18 months for subjects who choose to continue the daily device usage for 6 or 9 additional months) | 
| Safety of daily at-home light and sound stimulation: questionnaire | Safety of daily at-home light and sound stimulation will be assessed by using a daily questionnaire that asks for any adverse effects of the stimulation. The daily questionnaires will be collected and assessed at the interim analysis time point (Month 1) and later time points (Month 6 or 9 and Month 12 or 18). | Over 6 or 9 months (or over 12 or 18 months for subjects who choose to continue the daily device usage for 6 or 9 additional months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, Cognitive Impairment, Non-invasive Sensory Stimulation, Light and Sound Stimulation, Gamma