Sensory-Evoked Cortical Gamma Oscillation for Alzheimer's Disease

Overseen By Roberto Fernandez-Romero, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Tennessee Medical Center

Disqualifiers: Severe dementia, Other neurodegenerative, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment GammaSense Stimulation device for Alzheimer's Disease?

Research shows that using the GammaSense Stimulation device, which involves 40 Hz sensory stimulation, can reduce Alzheimer's disease markers like amyloid and tau levels, improve brain connectivity, and maintain daily living activities in patients. Studies in both animals and humans suggest that this treatment is safe and may help slow down the progression of Alzheimer's disease. ^{1 2 3 4 5}

Is the 40-Hz Gamma Oscillation Therapy safe for humans?

Research shows that 40-Hz Gamma Oscillation Therapy, also known as GENUS, is generally safe for humans. Studies involving Alzheimer's patients have found it to be well-tolerated, with high adherence to daily treatment and no significant safety concerns reported. ^{1 2 3 4 6}

How does the GammaSense Stimulation treatment differ from other Alzheimer's treatments?

The GammaSense Stimulation treatment is unique because it uses non-invasive sensory stimulation to induce 40 Hz gamma oscillations in the brain, which may reduce Alzheimer's disease pathology and improve cognitive function. Unlike traditional drug treatments, this therapy focuses on restoring brain wave patterns to potentially modify the disease's progression. ^{1 2 3 4 7}

What is the purpose of this trial?

The purpose of the study is to investigate the efficacy of cortical gamma oscillation on visual sensory processing and cognitive function in Alzheimer's Disease (AD) patients by combining a therapeutic sensory stimulation device capable of evoking 40-Hz gamma oscillation via non-invasive visual and auditory stimulation with pre-established markers of cortical network activity, i.e., electroencephalography (EEG) and event-related potentials (ERP), to evaluate the applicability of the 40-Hz multimodel sensory stimulation as a novel therapeutic approach for treatment of AD patients.

Research Team

Roberto Fernandez-Romero, MD

Principal Investigator

University of Tennessee Medical Center

Eligibility Criteria

This trial is for English-speaking individuals aged 60 or older with a confirmed diagnosis of Alzheimer's Disease. Participants must be able to consent for themselves and may need to undergo a Lumbar Puncture if they haven't been tested for specific AD markers. It excludes those with severe dementia, incompatible implants like pacemakers, other cognitive impairments, or claustrophobia requiring medication.

Inclusion Criteria

I understand the details of this clinical trial and can make decisions about my care.

I am 60 or older and have been diagnosed with Alzheimer's Disease.

Fluent and literate in English language

Exclusion Criteria

I need medication to manage my claustrophobia.

I have severe memory loss that affects my daily life.

You have a pacemaker or other implants that may not work with MRI scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one hour daily gamma frequency sensory stimulation from the investigational device for an 8 week period

8 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with neurophysiological testing repeated 4 weeks following the conclusion of therapy

4 weeks

Treatment Details

Interventions

• GammaSense Stimulation device

Trial Overview The study tests the GammaSense Stimulation device that uses visual and auditory stimulation to evoke gamma oscillation in the brain. The goal is to improve sensory processing and cognitive function in Alzheimer's patients, measured by EEG and ERP.

Participant Groups

Group I: AD Patients Experimental Treatment 1 Intervention

Patients with Alzheimer's Disease, as verified by positive A(beta)-PET and/or CSF tau/A(beta) biomarkers, who will receive one hour daily gamma frequency sensory stimulation from the investigational device for an 8 week period.

Who Is Running the Clinical Trial?

University of Tennessee Medical Center

Lead Sponsor

Trials

7

Recruited

450+

Findings from Research

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]

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]

Sensory gamma entrainment may offer a new therapeutic approach for reducing amyloid β peptide (Aβ) accumulation, a key feature in Alzheimer's disease (AD).

The review discusses how sensory gamma entrainment could improve AD by targeting Aβ clearance pathways and addresses the potential mechanisms and stimulus parameters involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism. Hu, J., Zheng, L., Guan, Z., et al.[2023]

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]

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]

References

1. 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]

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

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

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

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

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

Sensory gamma entrainment: Impact on amyloid protein and therapeutic mechanism. [2023]

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

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

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]