Clinical trial NCT04042922: High Frequency Light and Sound Stimulation to Improve Brain Functions in Alzheimer's Disease
Official title: Acute Treatment of Alzheimer's Disease With Gamma Frequency Stimulation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Cognitive Impairment
Non-invasive Sensory Stimulation
Light and Sound Stimulation
Gamma
Lead sponsor: Massachusetts Institute of Technology
Sponsor class: OTHER
First posted: 2019-08-02
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Feasibility of gamma frequency stimulation
timeFrame: Immediately after the completion of the stimulation
measure: Tolerability of gamma frequency stimulation
timeFrame: Immediately after the completion of the stimulation
measure: Safety of gamma frequency stimulation
timeFrame: Immediately after the completion of the stimulation
Secondary outcomes:
Other outcomes:
measure: Changes in working memory after gamma frequency stimulation
timeFrame: Baseline and immediately after the completion of the stimulation
Locations:
city: Cambridge
country: United States
facility: Massachusetts Institute of Technology
state: Massachusetts
Study officials:
affiliation: Massachusetts Institute of Technology
name: Li-Huei Tsai, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts Institute of Technology
name: Edward S Boyden, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts Institute of Technology
name: Diane Chan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.
citation: Martorell AJ, Paulson AL, Suk HJ, Abdurrob F, Drummond GT, Guan W, Young JZ, Kim DN, Kritskiy O, Barker SJ, Mangena V, Prince SM, Brown EN, Chung K, Boyden ES, Singer AC, Tsai LH. Multi-sensory Gamma Stimulation Ameliorates Alzheimer's-Associated Pathology and Improves Cognition. Cell. 2019 Apr 4;177(2):256-271.e22. doi: 10.1016/j.cell.2019.02.014. Epub 2019 Mar 14.
citation: Adaikkan C, Middleton SJ, Marco A, Pao PC, Mathys H, Kim DN, Gao F, Young JZ, Suk HJ, Boyden ES, McHugh TJ, Tsai LH. Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection. Neuron. 2019 Jun 5;102(5):929-943.e8. doi: 10.1016/j.neuron.2019.04.011. Epub 2019 May 7.