GENUS Stimulation to Prevent Alzheimer's Disease

Recruiting at 1 trial location

Overseen By Diane Chan, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: NMDA antagonists, Warfarin

Disqualifiers: Epilepsy, Renal disease, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 months

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new light and sound device called GENUS (Gamma Entrainment Using Sensory stimulation) that may help prevent Alzheimer's disease by boosting brain activity related to memory. The device uses gentle light and sound to increase gamma waves, which are often reduced in people at risk for Alzheimer's. Suitable candidates for this trial have a family history of Alzheimer's and experience memory changes that do not yet impact daily life. Participants must also be comfortable with brain scans and providing blood samples. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new preventive strategies for Alzheimer's disease.

Will I have to stop taking my current medications?

The trial requires that participants do not take NMDA antagonists. If you are undergoing a lumbar puncture, you cannot use warfarin or similar blood thinners. Other medications are not specifically mentioned, so check with the study team for more details.

What prior data suggests that this device is safe for preventing Alzheimer's disease?

Research shows that the GENUS device, which uses 40Hz light and sound, is generally well-tolerated by people with Alzheimer's disease. Studies have found that daily use of this device for up to six months is safe. In fact, some patients with mild Alzheimer's have used it safely every day for two years. These findings suggest that the GENUS device could be a safe option for helping prevent dementia in those at risk for Alzheimer's. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the GENUS light and sound device because it offers a novel approach to potentially preventing Alzheimer's disease. Unlike traditional treatments that often rely on medications targeting brain chemistry, GENUS uses a unique method of brain stimulation. This device delivers light and sound at a 40Hz frequency, which is thought to influence brain waves and possibly slow the progression of Alzheimer's. This non-invasive technique could provide an innovative, drug-free alternative to managing or preventing the condition.

What evidence suggests that this device is effective for preventing Alzheimer's disease?

In this trial, participants will receive either an active or sham version of the GENUS device. Studies have shown that a 40Hz light and sound device, like the active GENUS, can aid in managing Alzheimer's disease. Research indicates that this type of stimulation can reduce harmful proteins in the brain, such as amyloid and tau, which are linked to Alzheimer's. Early findings suggest that daily use of this device might slow memory loss and other symptoms. Specifically, a small study found that people using 40Hz stimulation for two years experienced fewer declines in memory and brain health. This method is safe and can be used at home, making it a promising option for those at risk of developing Alzheimer's. ^{1 2 5 6 7}

Who Is on the Research Team?

Diane Chan, MD PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for cognitively normal people aged 55-90 with a family history of Alzheimer's, who have certain scores on memory and mental state exams, and specific brain amyloid levels. They must be able to undergo MRI/PET scans, have good vision and hearing for tests, and can't be pregnant or have severe illnesses that affect study participation.

Inclusion Criteria

Able to comply with neuropsychological testing and other study procedures in opinion of site PI

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

My immediate family has a history of Alzheimer's disease.

Exclusion Criteria

Laboratory findings, if known (study does not perform testing) suggestive of systemic illness such as renal disease

I have a brain condition like fluid buildup or a tumor.

I don't have bleeding disorders or low platelet levels if I agree to undergo a lumbar puncture.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants use the GENUS light and sound device at home for 12 months, 60 minutes each day

12 months

4-6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• GENUS

Trial Overview

The GENUS device uses light and sound at 40Hz to stimulate gamma waves in the brain. The study aims to see if this stimulation can prevent dementia in those at risk for Alzheimer's by reducing toxic proteins in the brain associated with memory loss.

How Is the Trial Designed?

Group I: Active GENUS light and sound Active Control 1 Intervention

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.

Group II: Sham GENUS light and sound Placebo Group 1 Intervention

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

GENUS is already approved in United States for the following indications:

Approved in United States as GENUS for:

• Investigational for prevention of dementia in people at risk for Alzheimer's disease

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Massachusetts Institute of Technology

Collaborator

Trials

104

Recruited

12,810,000+

Published Research Related to This Trial

Gamma entrainment through non-invasive auditory stimulation at 40 Hz has shown potential in enhancing beta amyloid uptake and improving cognitive symptoms in Alzheimer's disease, making it a promising therapeutic approach.

A study involving 13 elderly participants with memory complaints recorded EEG signals during auditory stimulation, providing valuable data for understanding brain oscillatory activity and its implications for dementia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive auditory brain stimulation for gamma-band entrainment in dementia patients: An EEG dataset. Lahijanian, M., Sedghizadeh, MJ., Aghajan, H., et al.[2022]

The GENUS device, which uses 40Hz sensory stimulation, was found to be safe and effective in inducing brain entrainment in both cognitively normal individuals and patients with mild Alzheimer's disease (AD) during a Phase 1 feasibility study involving 43 participants.

In a Phase 2A pilot study with 15 patients, chronic daily 40Hz stimulation led to significant improvements in brain health, including reduced hippocampal atrophy and better cognitive performance, suggesting its potential as a novel treatment for AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies. Chan, D., Suk, HJ., Jackson, BL., et al.[2023]

A 6-month study involving 22 patients with mild to moderate Alzheimer's disease showed that daily 40 Hz gamma sensory stimulation therapy was well tolerated and helped maintain functional abilities, unlike the sham group which experienced a decline.

Patients receiving the active treatment had improved sleep quality, as indicated by reduced nighttime activity, suggesting that gamma sensory stimulation may have beneficial effects on both sleep and cognitive function in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients. Cimenser, A., Hempel, E., Travers, T., et al.[2021]

Daily exposure to 40 Hz synchronized sound and light stimuli for 2 weeks significantly improved hippocampal long-term potentiation (LTP) in three rat models of early Alzheimer's disease, suggesting a potential therapeutic effect.

The improvement in LTP was linked to a reduction in pro-inflammatory mechanisms, as indicated by a negative correlation with active caspase-1 levels, highlighting the importance of inflammation in the treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease. Yang, Y., Ondrejcak, T., Hu, NW., et al.[2023]

Gamma Entrainment Using Sensory stimulation (GENUS) shows promise as a non-pharmacological treatment for Alzheimer's disease, with animal studies indicating it can positively affect cognitive decline and reduce amyloid plaques and neurofibrillary tangles.

Although research on GENUS in humans is still in early stages, initial findings suggest it is feasible and warrants further investigation to establish its effectiveness as a disease-modifying intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. Manippa, V., Palmisano, A., Filardi, M., et al.[2023]

In a study investigating auditory stimulation methods, 40 Hz sinusoidal sounds produced the strongest neural response in the prefrontal region when participants' eyes were closed, suggesting enhanced cognitive engagement.

The use of 40 Hz square wave sounds was found to suppress alpha rhythms, indicating a potential new approach to auditory entrainment that could improve cognitive performance and help prevent cerebral atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of the neural response during 40 Hz auditory entrainment in closed-eye state in human prefrontal region. Han, C., Zhao, X., Li, M., et al.[2023]

In a study involving 15 participants and one epilepsy patient, incorporating cognitive tasks during Gamma ENtrainment Using Sensory stimulation (GENUS) sessions enhanced the strength and reach of gamma brainwave responses, particularly affecting deep brain areas like the hippocampus.

This suggests that adding cognitive workload to GENUS therapy could improve its effectiveness for Alzheimer's disease treatment by better engaging critical brain regions associated with memory and cognition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive tasks propagate the neural entrainment in response to a visual 40 Hz stimulation in humans. Khachatryan, E., Wittevrongel, B., Reinartz, M., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05655195

Chronic Treatment of Alzheimer's Disease by Gamma Light ...

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 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9797689/

An update on the use of gamma (multi)sensory stimulation for ...

This review summarizes the evidence on GENUS effectiveness, from animal models to AD patients.

3.

picower.mit.edu

picower.mit.edu/news/small-study-suggests-40hz-sensory-stimulation-may-benefit-some-alzheimers-patients-years

Small study suggests 40Hz sensory stimulation may benefit ...

“We found that daily 40Hz audiovisual stimulation over 2 years is safe, feasible, and may slow cognitive decline and biomarker progression, ...

4.

journals.plos.org

journals.plos.org/plosone/article?id=10.1371/journal.pone.0278412

Gamma frequency sensory stimulation in mild probable ...

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents ...

5.

alz-journals.onlinelibrary.wiley.com

alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.70792

Gamma sensory stimulation in mild Alzheimer's dementia: An ...

These findings suggest that long-term 40 Hz audiovisual stimulation is safe, feasible, and may offer cognitive and biomarker benefits in some ...

6.

picower.mit.edu

picower.mit.edu/news/review-evidence-expanding-40hz-gamma-stimulation-promotes-brain-health

Review: Evidence expanding that 40Hz gamma stimulation ...

... 40Hz stimulation as “GENUS” for Gamma Entrainment Using Sensory Stimulation. ... gamma sensory stimulation can combat Alzheimer's pathology.

7.

rally.massgeneralbrigham.org

rally.massgeneralbrigham.org/study/genusprevention

GENUS Study: Can we prevent Alzheimer's disease using ...

Our work shows that our device, GENUS, is well tolerated and can slow down progression of disease in patients with mild AD. Since our device is safe and so easy ...