Clinical trial NCT05776641: Gamma Light and Sound Stimulation to Prevent Dementia in Cognitively Normal People At Risk for Alzheimer's Disease
Official title: Prevention of Alzheimer's Disease Using Gamma Entrainment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Family Members
Keywords: Cognitively normal
Alzheimer's disease
Gamma
Amyloid
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Massachusetts Institute of Technology
First posted: 2023-03-20
Enrollment: 200
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: The investigators are recruiting participants aged 55+ with normal memory who have or had a close family member with Alzheimer's disease. 200 participants will undergo a blood test and a subset will undergo an amyloid PET scan and only 50 participants who have cerebral amyloid deposits will continue in the study. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for 12 months at home, for 60 minutes each day when they are awake. Participants will come to the Massachusetts General Hospital in Boston for 4-6 visits: before starting the stimulation, at 6 months, and after 12 months of usage. The participants will undergo PET scans, MRI, EEG, blood tests and memory tests and questionnaires at each visit to monitor progress. In addition, people may elect to allow for us to study their cerebral spinal fluid. Participants will also wear a "fitbit" like watch to monitor sleep and activity throughout the study. The goal of this study is to evaluate whether stimulation with our device at 40Hz will reduce AD pathology in the brain.

Eligibility criteria: Inclusion Criteria:

1. Between 55 - 90 years of age, inclusive.
2. Immediate family history of Alzheimer's disease.
3. Mini-Mental State Exam (MMSE) score of 27 or greater at baseline or expected score range for cognitively normal adjusted for education level.
4. Clinical Dementia Rating Global Score of 0 at baseline.
5. 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.
6. Low serum amyloid levels at baseline.
7. Elevated fibrillar amyloid using 11C PiB PET at baseline between 20 - 70 CL.
8. Willing and able to undergo MRI brain and PET brain scans.
9. Adequate visual and auditory acuity to allow for neuropsychological testing.
10. Able to comply with neuropsychological testing and other study procedures in opinion of site PI.
11. Willing and able to complete baseline assessments, and willing to participate in 13-month study protocol.
12. Willing to provide blood samples at specified timepoints. Willing to consider contributing CSF samples at specified timepoints, if asked.

Exclusion Criteria:

1. 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.
2. High myopia \< -7 diopters, or untreated cataracts that affect vision.
3. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the study protocol.
4. For subjects agreeing to undergo lumbar punctures, history of bleeding disorders or laboratory results indicating low platelet levels are exclusionary for the procedure.
5. Concomitant medications:

   1. Treatment with NMDA antagonists.
   2. For subjects undergoing lumbar puncture, current use of warfarin or similar anti-coagulants is exclusionary for the procedure.
6. Clinical conditions:

   1. History of seizure or medical diagnosis of epilepsy.
   2. Female subjects who are pregnant or currently breastfeeding.
   3. History of severe allergic or anaphylactic reactions.
   4. 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.
   5. Neurodegenerative disorder associated with cognitive impairment.
   6. Renal disease.
7. 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:

   1. Severe leukoencephalopathy seen on MRI.
   2. Relevant structural abnormality (i.e., normal pressure or obstructive hydrocephalus, hypoxic ischemic lesions, hemorrhages, tumors, malformations).
   3. Cerebral amyloid angiopathy, evidenced by T2\* or other susceptibility weighted-MRI.
8. Laboratory findings, if known (study does not perform testing) suggestive of systemic illness such as renal disease.
9. Site investigator's discretion, if s/he feels the subject cannot complete sufficient key study procedures. Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the Project Director.

Primary outcomes:
measure: Changes in brain amyloid deposition over the study period, as measured by PiB PET.
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: Changes in brain tau deposition
timeFrame: Baseline to 12 months
measure: Changes in brain structure using structural MRI
timeFrame: Baseline to 12 months
measure: Changes in brain electrical activity
timeFrame: Baseline to 12 months
measure: Changes in brain connectivity by functional MRI
timeFrame: Baseline to 12 months
measure: Changes to rest-activity parameters using actigraphy.
timeFrame: Baseline to 12 months
measure: Changes in blood biomarkers of AD
timeFrame: Baseline to 12 months
measure: Compliance of usage as measured by timestamp tracking and eye-tracking technology
timeFrame: Baseline to 12 months
measure: Change from baseline in CSF levels of amyloid and tau.
timeFrame: Baseline to 12 months
Other outcomes:
measure: Changes in CSF flow, as measured by BOLD fMRI
timeFrame: Baseline to 12 months
measure: Change from baseline in integrity of white matter tracks and myelination as measured by diffusion MR imaging.
timeFrame: Baseline to 12 months
measure: Changes in performance on memory tasks, particularly those that are reliant on visual or auditory pathways, using a neuropsychological test battery.
timeFrame: Baseline to 12 months
measure: Change from baseline in gamma oscillations as measured by EEG
timeFrame: Baseline to 12 months
measure: Change from baseline in sleep
timeFrame: Baseline to 12 months
measure: Change from baseline in activity levels
timeFrame: Baseline to 12 months
measure: Incidence of adverse events
timeFrame: Baseline to 12 months
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cambridge
country: United States
facility: Massachusetts Institute of Technology
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Diane Chan, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: