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

Primary Purpose

Alzheimer Disease

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

GENUS device (Active Settings)

GENUS device (Sham Settings)

About this trial

This is an interventional supportive care trial for Alzheimer Disease focused on measuring Alzheimer Disease, Cognitive Impairment, Non-invasive Sensory Stimulation, Light and Sound Stimulation, Gamma

Eligibility Criteria

50 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Massachusetts Institute of Technology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Exposure to active stimulation for 30 - 60 min

Exposure to control stimulation for 30 - 60 min

Arm Description

Subjects in this arm will receive 30 - 60 minutes of active stimulation

Subjects in this arm will receive 30 - 60 minutes of control stimulation

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04042922

First Posted

July 24, 2019

Last Updated

September 13, 2021

Sponsor

Massachusetts Institute of Technology

1. Study Identification

Unique Protocol Identification Number

NCT04042922

Brief Title

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

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Unknown status

Study Start Date

April 19, 2019 (Actual)

Primary Completion Date

April 30, 2023 (Anticipated)

Study Completion Date

April 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Massachusetts Institute of Technology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

Keywords

Alzheimer Disease, Cognitive Impairment, Non-invasive Sensory Stimulation, Light and Sound Stimulation, Gamma

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Exposure to active stimulation for 30 - 60 min

Arm Type

Experimental

Arm Description

Subjects in this arm will receive 30 - 60 minutes of active stimulation

Arm Title

Exposure to control stimulation for 30 - 60 min

Arm Type

Sham Comparator

Arm Description

Subjects in this arm will receive 30 - 60 minutes of control stimulation

Intervention Type

Device

Intervention Name(s)

GENUS device (Active Settings)

Other Intervention Name(s)

Gamma frequency stimulation, Light and sound stimulation

Intervention Description

Participants in the experimental group will use the GENUS device configured to active settings for 30 - 60 minutes.

Intervention Type

Device

Intervention Name(s)

GENUS device (Sham Settings)

Other Intervention Name(s)

Gamma frequency stimulation, Light and sound stimulation

Intervention Description

Participants in the control group will use the GENUS device configured to sham settings for 30 - 60 minutes.

Primary Outcome Measure Information:

Title

Feasibility of gamma frequency stimulation

Description

Time Frame

Immediately after the completion of the stimulation

Title

Tolerability of gamma frequency stimulation

Description

Tolerability of gamma frequency stimulation will be assessed by using a questionnaire asking for the subjects' overall experience with the stimulation.

Time Frame

Immediately after the completion of the stimulation

Title

Safety of gamma frequency stimulation

Description

Safety of gamma frequency stimulation will be assessed by using a questionnaire asking for any adverse effects of the stimulation.

Time Frame

Immediately after the completion of the stimulation

Other Pre-specified Outcome Measures:

Title

Changes in working memory after gamma frequency stimulation

Description

Exploratory measure to check if there is any change in n-back test performance, between baseline and immediately after the completion of the stimulation. The n-back test involves a sequence of stimuli (e.g., letters, numbers), presented one at a time, and a subject is asked to indicate when the current stimulus is the same as the stimulus presented n times earlier in the sequence. The performance metrics will include the "hit" rate (number of correct responses out of total number of target stimuli; ranging from 0 to 1), "false alarm" rate (number of incorrect responses out of total number of non-target stimuli; ranging from 0 to 1), and response time.

Time Frame

Baseline and immediately after the completion of the stimulation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li-Huei Tsai, PhD

Organizational Affiliation

Massachusetts Institute of Technology

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Edward S Boyden, PhD

Organizational Affiliation

Massachusetts Institute of Technology

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Diane Chan, MD, PhD

Organizational Affiliation

Massachusetts Institute of Technology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts Institute of Technology

City

Cambridge

State/Province

Massachusetts

ZIP/Postal Code

02139

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27929004

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. Erratum In: Nature. 2018 Oct;562(7725):E1.

Results Reference

background

PubMed Identifier

30879788

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.

Results Reference

background

PubMed Identifier

31076275

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.

Results Reference

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

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