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

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Alzheimer's disease (AD) is characterized by significant memory loss and toxic protein deposits (amyloid and tau) in the brain. The investigators' lab found a non-invasive way to remove these toxic proteins from the brain in AD mouse models. Remarkably, treated mice also have improved memory on behavioral testing. The investigators aim to translate this non-invasive method, which uses light and sound to stimulate the brain, to be used in mild Alzheimer's patients. 40 participants with mild Alzheimer's disease will be recruited, and the investigators will assess their brain waves with electroencephalogram (EEG) before, during, and after light and sound stimulation for safety, feasibility, and to optimize the stimulation device for use in the mild AD population.

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.

Is the 40Hz Light and Sound Therapy safe for humans?

Studies show that 40Hz Light and Sound Therapy, also known as GENUS, is generally safe and well-tolerated in humans, with no reported side effects in small trials. ^{1 2 3 4 5}

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

The GENUS device is unique because it uses non-invasive light and sound therapy at 40Hz to stimulate brain activity, which may help reduce Alzheimer's disease symptoms by improving brain function and reducing harmful proteins. Unlike traditional drug treatments, this therapy focuses on enhancing brain oscillations to potentially modify the disease's progression. ^{2 3 4 6 7}

What data supports the effectiveness of the GENUS device, 40Hz Light and Sound Therapy, Gamma Light Therapy for Alzheimer's Disease?

Research shows that using 40Hz light and sound therapy can help reduce Alzheimer's disease symptoms by improving brain function and reducing harmful proteins in the brain. Studies in both animals and humans have shown that this treatment can improve memory, daily activities, and sleep quality in people with Alzheimer's. ^{2 3 4 5 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]

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 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 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]

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]

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. 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]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Feasibility Study of AlzLife 40 Hz Sensory Therapy in Patients with MCI and Early AD. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer's disease. [2022]

6. United States 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Study on the effect of 40 Hz non-invasive light therapy system. A protocol for a randomized, double-blinded, placebo-controlled clinical trial. [2023]