Clinical trial NCT05655195: Chronic Treatment of Alzheimer's Disease by Gamma Light and Sound Therapy
Official title: Chronic Treatment of Alzheimer's Disease With Gamma Frequency Stimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Alzheimer Disease, Early Onset
Alzheimer Disease, Late Onset
Alzheimer's Disease (Incl Subtypes)
Alzheimer's
Alzheimer's Disease
Keywords: Alzheimer's
Alzheimer
Alzheimer's disease
Light and Sound Stimulation
Tactile Stimulation
Lead sponsor: Massachusetts Institute of Technology
Sponsor class: OTHER
First posted: 2022-12-19
Enrollment: 50
Sex: ALL
Minimum age (years): 65
Maximum age (years): 100
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. The investigator's 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. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. For the present study, 60 participants with mild Alzheimer's disease will be enrolled and will use this light and sound device at-home daily for 6-months. Investigators will measure changes in brain waves with EEG, blood biomarkers, the microbiome via fecal samples, functional and structural MRI scans, memory and cognitive testing, and questionnaires at 3 in-person visits throughout the study. After the 6-month time point, participants will have the option of continuing in the study for one additional year and completing an 18-month study visit. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.

Detailed description: 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 investigator's 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. The investigators developed a light and sound device for humans that stimulates the brain at 40Hz that can be used safely at home. The investigators also developed a vibrating device for humans that stimulates the brain at 40Hz via tactile stimulation. The investigators want to see if using these devices can prevent dementia in people who are at risk for developing Alzheimer's disease.

The investigators are recruiting 60 participants who have been diagnosed with Alzheimer's disease to participate in this study. There will be a small cohort of 4 early-onset AD participants aged 50-65, and the rest will be diagnosed with typical AD and aged 65+. It will take place at the Massachusetts Institute of Technology in Cambridge, MA, and will last 6 months with 3 required visits to the institution: the first at baseline, the second at three months, and the last after six months. Visits will include blood tests, fecal samples, EEG (using light, sound, and tactile stimulation), MRI, memory and cognitive tests, and questionnaires to monitor progress. Participants will take home a gamma light and sound device to use daily as well as a "Fitbit" type of watch to wear to track sleep patterns. Half of the participants will receive sham treatment, meaning they will use the investigators' device but the light and sound will not be set at 40Hz. The other half will receive the same device but it will be set to stimulate the brain with 40Hz light and sound. Neither the participant nor the investigators will know whether the participant is receiving sham or active stimulation. Participants will use the device for six months at home, for 60 minutes each day when they are awake. After six months, participants will have the option of continuing in the study for one additional year, during which time they will be guaranteed the 40Hz active treatment, regardless of their original group assignment. For this additional year, participants will continue to use the device for 60 minutes every day, and they will come in for a final visit to MIT at the 18-month time point.

The purpose of this study is to determine whether gamma entrainment through non-invasive 40Hz sensory stimulation is possible in those with AD, and whether functional connectivity in their brain and molecular biomarkers of AD will change after 6 months of daily treatment with the investigators' light and sound device. The treatment's impact on the microbiome, cognition, and daily sleep and activity will also be measured. This study will provide critical insight into extended therapy involving non-invasive 40Hz sensory stimulation as a possible therapeutic strategy for mild to moderate Alzheimer's disease.

Eligibility criteria: Inclusion Criteria:

Subjects may be enrolled into the study if they meet all of the following criteria:

* Subject is between the ages of 65 - 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.
* Able to complete the 1st month of at home stimulation at their primary residence. If subjects plan to spend more than 1 week away from their primary residence during the trial, their inclusion must be assessed by the research team.

Exclusion Criteria:

Subjects who meet any of the following conditions will not be enrolled in the study:

* Subjects who do not have healthcare.
* Subjects who are currently taking amyloid reducing therapy.
* Subjects who have \> 4 cerebral microbleeds or 1 macrobleed in their brain
* Active treatment on a dosage of one or more psychiatric agents (e.g. antidepressants, antipsychotics, etc) for LESS THAN three months (a stable dose for greater than or equal to three months is ok).
* Subjects who are actively diagnosed with cancer and undergoing cancer-related treatments
* 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
* 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.
* Subjects with untreated or unstable depression
* Active treatment with one or more anti-epileptic agent.
* Subjects who have had a stroke within the past 24 months.
* Subjects who have had eye surgery in the last 3 months or are scheduled to have eye surgery in the next 6 months (during the study)
* Subjects diagnosed with migraine headache.
* 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.
* Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke, progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.

Primary outcomes:
measure: Feasibility of gamma frequency stimulation as assessed by a change of gamma frequency waves during EEG
timeFrame: Immediately after completing the stimulation at baseline, month 3, and month 6 visits
measure: Baseline incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
timeFrame: Immediately after the completion of the stimulation at baseline.
measure: Mid-point incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
timeFrame: Immediately after the completion of the stimulation at Month 3.
measure: Endpoint incidence of stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
timeFrame: Immediately after the completion of the stimulation at the end of the trial- Month 6 timepoints.
measure: Change in stimulation-related adverse symptoms and side effects as assessed by post-stimulation questionnaires
timeFrame: During weekly phone calls throughout the 6-month trial period
measure: Changes in functional brain connectivity as measured by changes in brain white matter on functional MRI scans
timeFrame: At baseline, month 3, and month 6 visits during MRI sessions
measure: Changes in functional brain connectivity as measured by changes in blood-oxygen-level-dependent (BOLD) signals on functional MRI scans
timeFrame: At baseline, month 3, and month 6 visits during MRI sessions
measure: Changes in gamma entrainment, as measured by the change in response to 40Hz frequency during EEG sessions
timeFrame: At baseline, month 3, and month 6 visits during EEG sessions
measure: Changes in molecular biomarkers in AD as measured by RNA sequencing data, particularly those related to inflammation and amyloid levels
timeFrame: Immediately after blood draw at baseline and month 6 visits
Secondary outcomes:
measure: Changes in the microbiome as measured by fecal samples
timeFrame: Immediately after fecal sample collection at baseline and month 6
measure: Changes in cognitive performance as assessed by scores on an Alzheimer's cognitive testing battery
timeFrame: Immediately after completion of cognitive batteries at baseline, month 3, and month 6 Visits
measure: Changes in sleep/wake patterns, as measured by actigraph watch analyses
timeFrame: Immediately after actigraph data download at baseline, month 3, and month 6
Other outcomes:
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
References: