Gamma Light and Sound Stimulation to Prevent Dementia in Cognitively Normal People At Risk for Alzheimer's Disease

NCT05776641 | Recruiting DMC FDA Device

• 1 other identifier: 2021P002885
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

Alzheimer's disease (AD) is characterized by significant memory loss, toxic protein deposits (amyloid and tau) in the brain, and changes in the gamma frequency band on EEG. Gamma waves are important for memory, and in patients with AD, there are fewer gamma waves in the brain. The Tsai lab found that boosting gamma waves in AD mouse models using light and sound stimulation at 40Hz not only reduced amyloid and tau in the brain, but also improved memory. A light and sound device was developed for humans that stimulates the brain at 40Hz that can be used safely at home. The goal of this study is to see if using this device can prevent dementia in people who are at risk for developing Alzheimer's disease.

Conditions

Alzheimer Disease; Family Members

Keywords

Cognitively normal; Alzheimer's disease; Gamma; Amyloid

Outcome Measures

Primary Outcomes (1)

• Changes in brain amyloid deposition over the study period, as measured by PiB PET.

  The investigators will evaluate changes from baseline in amyloid deposition by using Pittsburgh compound B (PiB) PET, which is a standard for AD trial biomarkers, to assess progression towards AD with active or sham treatment.

  Baseline to 12 months

Secondary Outcomes (8)

• Changes in brain tau deposition

  Baseline to 12 months

• Changes in brain structure using structural MRI

  Baseline to 12 months

• Changes in brain electrical activity

  Baseline to 12 months

• Changes in brain connectivity by functional MRI

  Baseline to 12 months

• Changes to rest-activity parameters using actigraphy.

  Baseline to 12 months

Other Outcomes (7)

• Changes in CSF flow, as measured by BOLD fMRI

  Baseline to 12 months

• Change from baseline in integrity of white matter tracks and myelination as measured by diffusion MR imaging.

  Baseline to 12 months

• Changes in performance on memory tasks, particularly those that are reliant on visual or auditory pathways, using a neuropsychological test battery.

  Baseline to 12 months

Study Arms (2)

Active GENUS light and sound

ACTIVE COMPARATOR

The device is a light and sound device that delivers light stimulation using light-emitting diodes (LED) and sound stimulation through a speaker, with a centrally-mounted tablet that plays videos for entertainment. The device will be positioned on an easel such that the tablet is eye level with the participant while they are sitting 5 feet away. The active device delivers light and sound at 40Hz rate.

Device: GENUS

Sham GENUS light and sound

SHAM COMPARATOR

The device is the same as the active device but it delivers light and sound at different frequencies.

Device: GENUS

Interventions

GENUS DEVICE

Participants will use the GENUS light and sound device at home for 60 minutes daily for 12 months

Active GENUS light and sound; Sham GENUS light and sound

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 55 - 90 years of age, inclusive.
• Immediate family history of Alzheimer's disease.
• Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
• Clinical Dementia Rating Global Score of 0 at baseline.
• Delayed Recall score on the Logical Memory IIa subtest of 8 to 15 at baseline or expected score range for cognitively normal adjusted for education level.
• Low serum amyloid levels at baseline.
• Elevated fibrillar amyloid using 11C PiB PET at baseline between 20 - 70 CL.
• Willing and able to undergo MRI brain and PET brain scans.
• Adequate visual and auditory acuity to allow for neuropsychological testing.
• Able to comply with neuropsychological testing and other study procedures in opinion of site PI.
• Willing and able to complete baseline assessments, and willing to participate in 13-month study protocol.
• Willing to provide blood samples at specified timepoints. Willing to consider contributing CSF samples at specified timepoints, if asked.

You may not qualify if:

• MRI contraindications, such as presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body.
• High myopia \< -7 diopters, or untreated cataracts that affect vision.
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
• Concomitant medications:
• Treatment with NMDA antagonists.
• Clinical conditions:
• History of seizure or medical diagnosis of epilepsy.
• Female subjects who are pregnant or currently breastfeeding.
• History of severe allergic or anaphylactic reactions.
• Longstanding premorbid history (i.e., longer than 10 years) of alcohol or substance abuse with continuous abuse up to and including the time that the symptoms leading to clinical presentation developed.
• Neurodegenerative disorder associated with cognitive impairment.
• Renal disease.
• MR imaging findings such as stroke, tumor, leukoencephalopathy that could preclude meaningful analyses of clinical and imaging data in the opinion of the site PI, such as:
• Severe leukoencephalopathy seen on MRI.
• Relevant structural abnormality (i.e., normal pressure or obstructive hydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Massachusetts Institute of Technology: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Massachusetts Institute of Technology

Cambridge, Massachusetts, 02139, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Diane Chan, MD PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

MJ Quay, MA

CONTACT

617-807-0856; mquay@mgb.org

Gabrielle de Weck, BS

CONTACT

617-258-7723; gdeweck@mit.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: March 20, 2023
• Study Start: January 10, 2024
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: January 10, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)