Vagus Nerve Stimulation for Alzheimer's Disease

Overseen By Elizabeth Riley, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Cornell University

Disqualifiers: Brain injury, Epilepsy, Concussion, others

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

Compensation: Varies

Number of Visits: 2

Duration: 15-45 minutes

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with Alzheimer's disease by stimulating the vagus nerve, potentially protecting the locus coeruleus area of the brain. Participants will use a small device on their ear, known as the t-VNS transcutaneous auricular vagus nerve stimulator, while engaging in games and tasks. This could provide insights into early brain changes associated with Alzheimer's. The trial suits individuals who can use a touchscreen, keyboard, and mouse, and are willing to undergo a 90-minute MRI scan. As an unphased study, this trial offers participants the opportunity to contribute to groundbreaking research that could lead to new understanding and treatments for Alzheimer's disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transcutaneous vagus nerve stimulation is safe for Alzheimer's patients?

Research has shown that transcutaneous auricular vagus nerve stimulation (t-VNS) is generally safe, with only mild and short-lasting side effects. Studies indicate that t-VNS may improve the brain's ability to process information. Reported side effects are mild and temporary, such as skin irritation where the device contacts the ear. Although evidence supports its safety, some studies suggest that further research on humans is necessary to fully understand any potential risks. Overall, t-VNS appears to be a well-tolerated option for those considering participation in trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the t-VNS transcutaneous auricular vagus nerve stimulator for Alzheimer's disease because it offers a novel approach by directly stimulating the vagus nerve. Unlike standard treatments that often focus on managing symptoms with medication, this device targets the vagus nerve to potentially improve cognitive function by engaging the brain's natural pathways. Additionally, the non-invasive nature of this treatment, which involves short-duration stimulation while patients engage in cognitive tasks, offers a unique delivery method that could enhance patient experience and compliance.

What evidence suggests that this vagus nerve stimulation is effective for Alzheimer's Disease?

Research has shown that transcutaneous vagus nerve stimulation (t-VNS) can enhance thinking and memory. In this trial, participants will receive short-duration t-VNS while engaging in cognitive tasks and games. Studies have found that t-VNS might improve brain connectivity and boost memory, which is crucial for conditions like Alzheimer's disease. It may also aid in spatial understanding and memory. Another review suggested that t-VNS could benefit Alzheimer's disease by influencing the brain-gut-microbiota (BGM) axis. Overall, early findings indicate that t-VNS could support brain health and improve cognitive skills. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Alzheimer's Disease. It focuses on early damage in a brain area called the locus coeruleus (LC). Participants should be able to undergo MRI scans and vagus nerve stimulation without any issues.

Inclusion Criteria

Able to speak and understand English

Willing and able to use a keyboard and mouse

I can have a 90-minute MRI scan at Cornell.

Exclusion Criteria

Recent concussion

Colorblindness

Use of street drugs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments including MRI, blood pressure testing, and cognitive tasks

1 day

1 visit (in-person)

Treatment

Participants receive short-duration vagus nerve stimulation while engaging in cognitive tasks

15-45 minutes

1 visit (in-person)

Follow-up

Participants are monitored for changes in cognitive performance and physiological responses

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• t-VNS transcutaneous auricular vagus nerve stimulator

Trial Overview

The study tests if stimulating the vagus nerve through the skin (using t-VNS) can affect LC health and cognitive function. Techniques like MRI, functional MRI, and pupillometry are used to measure outcomes.

How Is the Trial Designed?

Group I: Cornell University Experimental Treatment 1 Intervention

Short-duration (less than an hour) vagus nerve stimulation will be delivered while participants engage in cognitive tasks and games. This study also includes a 90-minute MRI, blood pressure testing, saliva collection for genetic analysis, sensory testing, and blood pressure/heart rate measurement.

Who Is Running the Clinical Trial?

Cornell University

Lead Sponsor

Trials

179

Recruited

14,090,000+

Published Research Related to This Trial

Transcutaneous auricular vagus nerve stimulation (taVNS) showed promising results in two patients with structural focal epilepsy, leading to seizure freedom in one patient after 4 weeks and significant reduction in seizures for the other after 20 weeks.

Both patients experienced improved quality of life with no significant adverse events reported, suggesting that taVNS could be a safe and effective treatment option for individuals with focal epilepsy and preserved cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. Shiraishi, H., Egawa, K., Murakami, K., et al.[2023]

Vagus nerve stimulation (VNS) was well tolerated over one year in a study of 17 patients with Alzheimer's disease, showing promising cognitive-enhancing effects with 41.2% of patients improving on the ADAS-cog scale.

After one year, there was no significant decline in mood, behavior, or quality of life, suggesting that VNS may be a safe long-term treatment option for cognitive decline in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year. Merrill, CA., Jonsson, MA., Minthon, L., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved visual memory performance in a study of 60 healthy individuals aged 18 to 24, compared to a control group that did not receive taVNS.

Despite the positive effects on visual memory, taVNS did not show a significant impact on fatigue levels, indicating that while it may enhance cognitive function, it does not alleviate feelings of tiredness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transcutaneous auricular vagus nerve stimulation on visual memory performance and fatigue. Yıldız, R., Özden, AV., Nişancı, OS., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) shows potential as a treatment for disorders of consciousness, particularly in patients with a minimally conscious state (MCS), as it significantly alters brain activity measured by EEG.

In patients with MCS, taVNS led to notable changes in both delta and beta brain wave energy across multiple regions, suggesting it may enhance brain connectivity and promote awakening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. Yifei, W., Yi, Y., Yu, W., et al.[2023]

In a pilot study involving 10 patients with Alzheimer's disease, vagus nerve stimulation (VNS) showed a positive effect on cognitive function, with 70% of patients improving on the Alzheimer's Disease Assessment Scale (ADAS-cog) and 90% on the Mini-Mental State Examination (MMSE) after 3 months.

VNS was well tolerated by patients, with only mild and transient side effects reported, suggesting it is a safe intervention for cognitive enhancement in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. Sjögren, MJ., Hellström, PT., Jonsson, MA., et al.[2022]

Vagus nerve stimulation (VNS) has been effectively used to treat conditions like intractable epilepsy and treatment-resistant depression, and new non-invasive methods like transcutaneous VNS (t-VNS) provide similar benefits without the risks associated with surgery.

t-VNS shows promise for improving cognitive function and neurocardiovascular stability, particularly in aging populations, by enhancing cerebral blood flow and regulating the body's parasympathetic responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"The Wandering Nerve Linking Heart and Mind" - The Complementary Role of Transcutaneous Vagus Nerve Stimulation in Modulating Neuro-Cardiovascular and Cognitive Performance. Dolphin, H., Dukelow, T., Finucane, C., et al.[2022]

Citations

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Both vagus nerve stimulation and auriculotherapy are effective in improving cognitive functions. •. It demonstrates that taVNS can improve cognitive performance ...

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The main reported outcomes of VNS in the dementia cases were enhanced cognitive functions, an increased functional connectivity of various brain regions ...

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In some cases, with early-onset or profound HI, where individuals have relied on lipreading, superior visuospatial abilities have been reported.

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frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1334887/full

Transcutaneous vagus nerve stimulation: a new strategy ...

This review explores the interaction between percutaneous vagus nerve stimulation and the BGM axis, emphasizing its potential effects on AD.

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clinicaltrials.gov/study/NCT07214194

Vagus Nerve Stimulation to Enhance Memory in Aging

Device : Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) ... Alzheimer's disease pathology (pTau217, pTau181, Aβ42:40). post ...

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Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

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Safety and feasibility of transcutaneous vagus nerve ...

VINCI-AD is an investigator-led, single-site, single-blind, sham-controlled crossover pilot study which aims to assess the safety and feasibility of tVNS in 40 ...