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 light and sound device that creates brain waves at 40Hz. It targets people aged 55+ with a family history of Alzheimer's disease. The device aims to boost brain waves to reduce harmful proteins and improve memory.

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.

Is GENUS (Gamma Entrainment Using Sensory stimulation) safe for humans?

Studies show that GENUS, which uses 40Hz light and sound stimulation, is generally safe and well-tolerated in humans, including those with mild Alzheimer's disease. Participants in trials experienced no significant adverse effects, and the treatment was well-received over periods of up to six months. ^{1 2 3 4 5}

How is the GENUS treatment different from other Alzheimer's treatments?

GENUS is unique because it uses non-invasive sensory stimulation with light and sound at 40Hz to improve brain function and reduce Alzheimer's disease markers, unlike traditional drug treatments. This approach aims to restore normal brain rhythms and improve cognitive and daily living activities without medication. ^{1 2 3 4 6}

What data supports the effectiveness of the treatment GENUS, Gamma Entrainment Using Sensory stimulation, 40Hz Light and Sound Stimulation, in preventing Alzheimer's disease?

Research shows that GENUS, which uses 40Hz light and sound stimulation, can reduce Alzheimer's disease markers like amyloid and tau in mice, and improve memory and daily activities in humans with mild Alzheimer's. Studies also found that this treatment is safe, well-tolerated, and can improve brain connectivity and reduce brain shrinkage in patients. ^{1 2 3 4 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

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

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

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 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]

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]

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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

An update on the use of gamma (multi)sensory stimulation for Alzheimer's disease treatment. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer's Disease Patients. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Non-invasive auditory brain stimulation for gamma-band entrainment in dementia patients: An EEG dataset. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Gamma frequency sensory stimulation in mild probable Alzheimer's dementia patients: Results of feasibility and pilot studies. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Enhancement of the neural response during 40 Hz auditory entrainment in closed-eye state in human prefrontal region. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cognitive tasks propagate the neural entrainment in response to a visual 40 Hz stimulation in humans. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease. [2023]