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

Study Overview
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Brief Summary
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Alzheimer's disease (AD) is characterized by significant memory loss and toxic protein deposits (amyloid and tau) in the brain. The investigators' lab found a non-invasive way to remove these toxic proteins from the brain in AD mouse models. Remarkably, treated mice also have improved memory on behavioral testing. The investigators aim to translate this non-invasive method, which uses light and sound to stimulate the brain, to be used in mild Alzheimer's patients. 40 participants with mild Alzheimer's disease will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) before, during, and after light and sound stimulation for safety, feasibility, and to optimize the stimulation device for use in the mild AD population.

Detailed Description
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It is known that Alzheimer's disease (AD) patients have significant disruptions in brain waves, especially the gamma frequency ( 30 - 100 Hz) waves. Recently, the investigators' lab found that gamma entrainment using light and sound stimulation, which the investigators call GENUS, improves memory and decreases toxic accumulation of amyloid and tau in AD mouse models. This study aims to translate these findings in the mouse models to be used in mild Alzheimer's patients. The investigators will recruit 40 patients diagnosed with mild AD who will be randomly assigned to two study arms. Cognitive and mental health evaluations as well as memory tests will be performed on all subjects. All subjects will also be exposed to the GENUS device, which can deliver light and sound waves at different frequencies. The GENUS device is composed of a panel with light-emitting diode (LED) illumination and speakers for auditory stimulation. Each of the 2 groups will have different combinations of light and sound settings. The investigators will use electroencephalography (EEG) to check for how the participant's brain waves respond to the stimulation, and use questionnaires to evaluate for safety and tolerability.

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

Conditions
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Alzheimer Disease

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. 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 1 year. 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 2 years. 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exposure to active stimulation for 30 - 60 min<br>Subjects in this arm will receive 30 - 60 minutes of active stimulation | Device: GENUS device (Active Settings)<br>* Participants in the experimental group will use the GENUS device configured to active settings for 30 - 60 minutes.<br>* Other names: Light and sound stimulation;|
| Sham Comparator: Exposure to control stimulation for 30 - 60 min<br>Subjects in this arm will receive 30 - 60 minutes of control stimulation | Device: GENUS device (Sham Settings)<br>* Participants in the control group will use the GENUS device configured to sham settings for 30 - 60 minutes.<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 gamma frequency stimulation | Feasibility of gamma frequency stimulation in subjects with mild AD will be assessed by analyzing the EEG data from each subject for a sign of change in gamma frequency waves and determining the percent of subjects who show this change. | Immediately after the completion of the stimulation | 
| Tolerability of gamma frequency stimulation | Tolerability of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation. | Immediately after the completion of the stimulation | 
| Safety of gamma frequency stimulation | Safety of gamma frequency stimulation will be assessed by using a questionnaire asking for any adverse effects of the stimulation. | Immediately after the completion of the stimulation | 

 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