Brain Stimulation for Alzheimer's Disease

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts Institute of Technology

Must not be taking: NMDA antagonists, Seizure threshold reducers, Anti-epileptics, Psychiatric agents

Disqualifiers: Seizure, Stroke, Migraine, Suicide risk, 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: 2

Duration: 1 session

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with mild Alzheimer's disease, which often causes memory loss. The study uses the GENUS device, which combines light and sound to clear harmful proteins from the brain and improve memory, similar to results observed in mice. Researchers will check participants' brain waves using EEG (a test that measures electrical activity in the brain) before and after the stimulation to ensure safety and effectiveness. Individuals with mild Alzheimer's who are not currently on certain medications or have specific medical issues like seizures might find this trial suitable. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for Alzheimer's disease.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially if you are on NMDA receptor antagonists like Memantine, medications that lower seizure threshold, anti-epileptic agents, or psychiatric medications like antidepressants or antipsychotics. The trial does not specify a washout period, but these medications are part of the exclusion criteria.

What prior data suggests that this brain stimulation method is safe for Alzheimer's patients?

Research has shown that the GENUS device, which uses light and sound therapy, is generally safe for individuals with mild Alzheimer's disease. Studies have found that this therapy is well-tolerated, with most participants experiencing no serious side effects. For example, one study found that daily use of the GENUS device at home was safe and practical. Another study confirmed these findings, demonstrating that participants could use the device daily without major issues. Overall, the evidence suggests that the device is safe for brain stimulation in people with mild Alzheimer's. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for Alzheimer's, which often rely on medications to manage symptoms, the GENUS device uses brain stimulation as a novel approach. This device delivers targeted electrical stimulation to specific brain areas, potentially improving cognitive function without the systemic side effects associated with drugs. Researchers are excited because this non-invasive method might offer a new way to slow down or even improve the progression of Alzheimer's, offering hope for more effective management of the disease.

What evidence suggests that the GENUS device is effective for Alzheimer's disease?

Research has shown that the GENUS device, which uses light and sound therapy at 40 Hz, may help treat mild Alzheimer's disease. Studies have found that this therapy can reduce harmful protein buildup in the brain and improve memory in animals. In human studies, participants experienced less brain shrinkage and healthier brain connections after six months. Some research also suggests that this therapy might safely slow Alzheimer's progression over a few years. In this trial, participants will receive either active stimulation with the GENUS device or control stimulation. While results can vary, these studies indicate that the GENUS device could offer a new way to manage Alzheimer's symptoms. ^{2 3 4 6 7}

Who Is on the Research Team?

Li-Huei Tsai, PhD

Principal Investigator

Massachusetts Institute of Technology

Diane Chan, MD, PhD

Principal Investigator

Massachusetts Institute of Technology

Edward S Boyden, PhD

Principal Investigator

Massachusetts Institute of Technology

Are You a Good Fit for This Trial?

This trial is for individuals aged 50-100 with mild Alzheimer's Disease, having a Mini Mental State Exam score of 19-26. Participants must consent to the study; if unable, a legal representative can consent for them. Excluded are those without healthcare, on certain medications like NMDA antagonists or anti-seizure drugs, recent stroke survivors, pregnant women, and those with severe hearing or visual impairments.

Inclusion Criteria

Subject is willing to sign informed consent document

If I can't consent, someone legally allowed will do it for me.

I am between 50 and 100 years old.

Exclusion Criteria

You have had a serious risk of suicide or attempted suicide in the past year.

I have had a seizure or been diagnosed with epilepsy in the last 2 years.

I have had a stroke in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 30-60 minutes of either active or control gamma frequency stimulation using the GENUS device

1 session

1 visit (in-person)

Follow-up

Participants are monitored for safety, feasibility, and tolerability immediately after stimulation

Immediately after treatment

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• GENUS device

Trial Overview The GENUS device is being tested in this trial. It uses light and sound stimulation aimed at improving brain functions in patients with mild Alzheimer's disease. The study will monitor brain waves before, during, and after using the device to evaluate safety and effectiveness.

How Is the Trial Designed?

Group I: Exposure to active stimulation for 30 - 60 min Experimental Treatment 1 Intervention

Subjects in this arm will receive 30 - 60 minutes of active stimulation

Group II: Exposure to control stimulation for 30 - 60 min Placebo Group 1 Intervention

Subjects in this arm will receive 30 - 60 minutes of control stimulation

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

Who Is Running the Clinical Trial?

Massachusetts Institute of Technology

Lead Sponsor

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 non-invasive 40 Hz sensory therapy using light and sound was found to be safe and tolerable in a small group of 27 participants with Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD), with 11 completing 6 months of therapy.

Some participants showed cognitive improvements, with 2 out of 4 with subjective complaints and 2 out of 6 with AD improving their Montreal Cognitive Assessment (MOCA) scores, suggesting potential benefits of this therapy that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. McNett, SD., Vyshedskiy, A., Savchenko, A., et al.[2023]

A study involving 10 patients with mild cognitive impairment due to Alzheimer's disease demonstrated that daily 1-hour sessions of gamma flicker stimulation (40 Hz) were safe, well-tolerated, and adhered to over 4 to 8 weeks.

Preliminary results indicated that this gamma flicker stimulation may positively influence neural activity and immune factors in the nervous system, suggesting potential benefits for further research in Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. He, Q., Colon-Motas, KM., Pybus, AF., et al.[2022]

The RGn500 device, which combines photonic and magnetic emissions, showed a neuroprotective effect in a mouse model of Alzheimer's disease when applied daily for 10 minutes, leading to memory restoration and normalization of key Alzheimer's markers.

This treatment demonstrated similar therapeutic efficacy to traditional pharmacological approaches, suggesting it could be a promising alternative for managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Blivet, G., Meunier, J., Roman, FJ., et al.[2022]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05655195

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

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

Gamma sensory stimulation in mild Alzheimer's dementia: An ... The same group also reported white matter preservation, reduced myelin loss, and less brain atrophy after 6 months of 40 Hz light and sound ...

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 ... “GENUS may be less effective in early onset Alzheimer's disease patients, potentially owing to broad pathological differences from late-onset ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11952037/

40 Hz multisensory stimulation therapy for cognitive impairment Studies on animals with AD indicate that 40 Hz audiovisual combined stimulation (GENUS) could be effective in enhancing key pathological ...

5. thebrighterside.news thebrighterside.news/post/new-study-finds-40hz-sensory-stimulation-may-benefit-some-alzheimers-patients-for-years/

New study finds 40Hz sensory stimulation may benefit ... MIT researchers report two-year results showing 40 Hz light and sound therapy may slow Alzheimer's progression safely.

6. neurosciencenews.com neurosciencenews.com/daily-light-sound-memory-alzheimers-29865/

Daily Light and Sound Therapy May Slow Alzheimer's ... Safe and Noninvasive: The GENUS 40Hz light-and-sound therapy was well tolerated and feasible for daily home use. Source: Picower Institute at ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36454969/

Gamma frequency sensory stimulation in mild probable ... Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both ...