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

NCT04042922 | Active Not Recruiting FDA Device

• 1 other identifier: 1902706647
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

Other Outcomes (1)

• Changes in working memory after gamma frequency stimulation

  Baseline and immediately after the completion of the stimulation

Study Arms (2)

Exposure to active stimulation for 30 - 60 min

EXPERIMENTAL

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

Device: GENUS device (Active Settings)

Exposure to control stimulation for 30 - 60 min

SHAM COMPARATOR

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

Device: GENUS device (Sham Settings)

Interventions

GENUS device (Active Settings) DEVICE

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

Also known as: Gamma frequency stimulation, Light and sound stimulation

Exposure to active stimulation for 30 - 60 min

GENUS device (Sham Settings) DEVICE

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

Also known as: Gamma frequency stimulation, Light and sound stimulation

Exposure to control stimulation for 30 - 60 min

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts Institute of Technology: lead

Study Sites (1)

Massachusetts Institute of Technology

Cambridge, Massachusetts, 02139, United States

Location

Related Publications (4)

• 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.

  PMID: 27929004 BACKGROUND

• 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.

  PMID: 30879788 BACKGROUND

• 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.

  PMID: 31076275 BACKGROUND

• Chan D, Suk HJ, Jackson BL, Milman NP, Stark D, Klerman EB, Kitchener E, Fernandez Avalos VS, de Weck G, Banerjee A, Beach SD, Blanchard J, Stearns C, Boes AD, Uitermarkt B, Gander P, Howard M 3rd, Sternberg EJ, Nieto-Castanon A, Anteraper S, Whitfield-Gabrieli S, Brown EN, Boyden ES, Dickerson BC, Tsai LH. Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies. PLoS One. 2022 Dec 1;17(12):e0278412. doi: 10.1371/journal.pone.0278412. eCollection 2022.

  PMID: 36454969 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Ultraviolet Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phototherapy; Therapeutics

Study Officials

• Li-Huei Tsai, PhD

  Massachusetts Institute of Technology

  PRINCIPAL INVESTIGATOR

• Edward S Boyden, PhD

  Massachusetts Institute of Technology

  PRINCIPAL INVESTIGATOR

• Diane Chan, MD, PhD

  Massachusetts Institute of Technology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: August 2, 2019
• Study Start: April 19, 2019
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)