Gamma Light and Sound Therapy for Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Massachusetts Institute of Technology
Must not be taking: Amyloid reducers, NMDA antagonists
Disqualifiers: Cancer, Seizure, Stroke, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
Do I have to stop taking my current medications for the trial?
The trial requires that you stop taking certain medications, such as amyloid reducing therapy, NMDA receptor antagonists like Memantine, and medications that lower the seizure threshold. If you are on psychiatric medications, you must be on a stable dose for at least three months before joining the trial.
What data supports the effectiveness of the Gamma Light and Sound Therapy treatment for Alzheimer's Disease?
Research shows that 40 Hz sensory therapy, which includes light and sound, has improved cognitive scores in some Alzheimer's patients and is considered safe. Animal studies also suggest it may reduce Alzheimer's-related brain changes, and some participants reported benefits from the therapy.
12345Is Gamma Light and Sound Therapy safe for humans?
Small studies in humans have shown that 40 Hz sensory therapy using light and sound is safe and tolerable, with no reported side effects. Further research is needed to explore its effectiveness and feasibility.
12367How is the GENUS device treatment different from other Alzheimer's treatments?
The GENUS device treatment is unique because it uses non-invasive light and sound therapy at 40 Hz to stimulate brain activity, which may help improve cognitive function and daily living activities in Alzheimer's patients. Unlike traditional drug treatments, this therapy aims to restore normal brain oscillations and has shown promise in both animal and early human studies without reported side effects.
13589Eligibility Criteria
This trial is for individuals aged 50-100 with mild Alzheimer's disease, having an MMSE score of 19-26. They must be able to give consent or have a representative do so and complete the first month at their primary residence. Excluded are those without healthcare, on certain Alzheimer's medications, unstable psychiatric treatments, seizure history within two years, significant suicide risk, behavioral issues affecting compliance, recent stroke or eye surgery candidates.Inclusion Criteria
If I can't consent, someone legally allowed will do it for me.
I am between 50 and 100 years old.
I have mild Alzheimer's with a specific cognitive test score.
+2 more
Exclusion Criteria
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 with behavioral problems such as aggression/agitation/impulsivity that might interfere with their ability to comply with protocol
Subjects who have >3 microbleeds/microhemmorhages in their brain
+15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants use a gamma light and sound device at-home daily for 6 months, with 3 in-person visits for assessments
6 months
3 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension (optional)
Participants may opt into continuation of treatment for one additional year with guaranteed 40Hz active treatment
12 months
1 visit (in-person) at 18 months
Participant Groups
The study tests a device called GENUS that uses light and sound at 40Hz aimed to stimulate brain waves in people with mild Alzheimer's disease. Participants will use this device daily for six months at home while undergoing various assessments including EEGs, MRIs, cognitive tests and questionnaires to evaluate its effects on brain function and memory.
2Treatment groups
Active Control
Placebo Group
Group I: Alzheimer's Active ArmActive Control1 Intervention
Exposure to active sensory stimulation (40Hz) for 60 minutes daily for the length of the trial (6 months).
Group II: Alzheimer's Control ArmPlacebo Group1 Intervention
Exposure to control stimulation (sham) for 60 minutes daily for the length of the trial (6 months).
GENUS device is already approved in United States for the following indications:
🇺🇸 Approved in United States as 40Hz Light and Sound Therapy for:
- Alzheimer's disease
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts Institute of TechnologyCambridge, MA
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Who Is Running the Clinical Trial?
Massachusetts Institute of TechnologyLead Sponsor
References
An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. [2023]Alzheimer's disease (AD) is characterized by reduced fast brain oscillations in the gamma band (γ, > 30 Hz). Several animal studies show that inducing gamma oscillations through (multi)sensory stimulation at 40 Hz has the potential to impact AD-related cognitive decline and neuropathological processes, including amyloid plaques deposition, neurofibrillary tangles formation, and neuronal and synaptic loss. Therefore Gamma Entrainment Using Sensory stimulation (GENUS) is among the most promising approaches for AD patients' treatment. This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients. Despite the application on human is in its infancy, the available findings suggest its feasibility for the treatment of AD. We discuss such results in light of parameter improvement and possible underlying mechanisms. We finally emphasize the need for further research for its development as a disease-modifying non-pharmacological intervention.
A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. [2022]We and collaborators discovered that flickering lights and sound at gamma frequency (40 Hz) reduce Alzheimer's disease (AD) pathology and alter immune cells and signaling in mice. To determine the feasibility of this intervention in humans we tested the safety, tolerability, and daily adherence to extended audiovisual gamma flicker stimulation.
A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. [2023]Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) are debilitating diseases that affect millions of individuals and have notoriously limited treatment options. One emerging therapy, non-invasive 40 Hz sensory therapy delivered through light and sound has previously shown promise in improving cognition in Alzheimer Disease (AD) rodent models. Small studies in humans have proven safe and tolerable, however exploration of feasibility and utility is limited. The purpose of this study is to examine the feasibility of this treatment in a human population through a smart tablet application that emits light and sound waves at 40 Hz to the user over the span of 1 h a day. Confirmation of entrainment of 40 Hz stimulation in the cerebral cortex was performed via EEG. 27 preliminary subjects with subjective cognitive complaints, Mild Cognitive Impairment, or AD were enrolled in the study; 11 participants completed 6 months of therapy. Of those that discontinued treatment, other health issues and difficulties with compliance were the most common causes. Participants were followed with Montreal Cognitive Assessment (MOCA) and Boston Cognitive Assessment (BOCA). For participants with subjective cognitive complaints, 2 of the 4 had improved MOCA score and 1 of 4 had improved BOCA score. For the participant with MCI, his MOCA score improved. For AD participants, 2 out of 6 had improved MOCA score and 3 of the 6 stayed stable, while 3 of 6 BOCA score improved. 4 of 11 participants specifically increased their MOCA scores in the Memory Index section. Of the 8 participants/caregivers able to speak to perceived usefulness of the study, 6 spoke to at least some level of benefit. Of these 6, 2 enrolled with subjective cognitive complaint, 1 had MCI, and 3 had AD. The therapy did not have reported side effects. However, those who did not finish the study experienced issues obtaining and operating a smart tablet independently as well as complying with the therapy. Overall, further exploration of this treatment modalities efficacy is warranted.
Research Note: A self-luminous light table for persons with Alzheimer's disease. [2020]Light can be used to consolidate sleep in individuals with Alzheimer's disease and related dementias, but the light delivery method is one of the greatest challenges for successful treatment. Based on our field observations, it was hypothesised that a self-luminous light table would be a practical way to deliver light because persons with Alzheimer's disease typically spend a significant amount of time sitting at tables. Compared to a baseline week, sleep percent and efficiency significantly increased and agitation and depression scores significantly decreased during the four intervention weeks. The self-luminous light table was an effective and practical method to deliver circadian-effective light to persons with Alzheimer's disease.
Tailored Lighting Intervention for Persons with Dementia and Caregivers Living at Home. [2022]Light therapy has shown promise as a nonpharmacological treatment to help regulate abnormal sleep-wake patterns and associated behavioral issues prevalent among individuals diagnosed with Alzheimer's disease and related dementia (ADRD). The present study investigated the effectiveness of a lighting intervention designed to increase circadian stimulation during the day using light sources that have high short-wavelength content and high light output.
Photobiomodulation for Alzheimer's Disease: Translating Basic Research to Clinical Application. [2021]One of the challenges in translating new therapeutic approaches to the patient bedside lies in bridging the gap between scientists who are conducting basic laboratory research and medical practitioners who are not exposed to highly specialized journals. This review covers the literature on photobiomodulation therapy as a novel approach to prevent and treat Alzheimer's disease, aiming to bridge that gap by gathering together the terms and technical specifications into a single concise suggestion for a treatment protocol. In light of the predicted doubling in the number of people affected by dementia and Alzheimer's disease within the next 30 years, a treatment option which has already shown promising results in cell culture studies and animal models, and whose safety has already been proven in humans, must not be left in the dark. This review covers the mechanistic action of photobiomodulation therapy against Alzheimer's disease at a cellular level. Safe and effective doses have been found in animal models, and the first human case studies have provided reasons to undertake large-scale clinical trials. A brief discussion of the minimally effective and maximum tolerated dose concludes this review, and provides the basis for a successful translation from bench to bedside.
Neuroprotective effect of a new photobiomodulation technique against Aβ25-35 peptide-induced toxicity in mice: Novel hypothesis for therapeutic approach of Alzheimer's disease suggested. [2022]Photobiomodulation was assessed as a novel treatment of Alzheimer's disease (AD) by the use of a new device RGn500 combining photonic and magnetic emissions in a mouse model of AD.
Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients. [2021]Pathological proteins contributing to Alzheimer's disease (AD) are known to disrupt normal neuronal functions in the brain, leading to unbalanced neuronal excitatory-inhibitory tone, distorted neuronal synchrony, and network oscillations. However, it has been proposed that abnormalities in neuronal activity directly contribute to the pathogenesis of the disease, and in fact it has been demonstrated that induction of synchronized 40 Hz gamma oscillation of neuronal networks by sensory stimulation reverses AD-related pathological markers in transgenic mice carrying AD-related human pathological genes. Based on these findings, the current study evaluated whether non-invasive sensory stimulation inducing cortical 40 Hz gamma oscillation is clinically beneficial for AD patients. Patients with mild to moderate AD (n = 22) were randomized to active treatment group (n = 14; gamma sensory stimulation therapy) or to sham group (n = 8). Participants in the active treatment group received precisely timed, 40 Hz visual and auditory stimulations during eye-closed condition to induce cortical 40 Hz steady-state oscillations in 1-h daily sessions over a 6-month period. Participants in the sham group were exposed to similar sensory stimulation designed to not evoke cortical 40 Hz steady-state oscillations that are observed in the active treatment patients. During the trial, nighttime activities of the patients were monitored with continuous actigraphy recordings, and their functional abilities were measured by Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale. Results of this study demonstrated that 1-h daily therapy was well tolerated throughout the 6-month treatment period by all subjects. Patients receiving gamma sensory stimulation showed significantly reduced nighttime active periods, in contrast, to deterioration in sleep quality in sham group patients. Patients in the sham group also showed the expected, significant decline in ADCS-ADL scores, whereas patients in the gamma sensory stimulation group fully maintained their functional abilities over the 6-month period. These findings confirm the safe application of 40 Hz sensory stimulation in AD patients and demonstrate a high adherence to daily treatment. Furthermore, this is the first time that beneficial clinical effects of the therapy are reported, justifying expanded and longer trials to explore additional clinical benefits and disease-modifying properties of gamma sensory stimulation therapy. Clinical Trial Registration: clinicaltrials.gov, identifier: NCT03556280.
Gamma Entrainment in a Large Retrospective Cohort: Implications for Photic Stimulation Therapy for Alzheimer's Disease. [2021]Studies on mice models of Alzheimer's disease (AD) have suggested potential therapeutic benefits of intermittent photic stimulation at 40 Hz.