Vagus Nerve Stimulation for Alzheimer's Disease

Overseen By Andy Bolender, B.A.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Disqualifiers: FmrI contraindications, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 sessions

50 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

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

What data supports the effectiveness of this treatment for Alzheimer's disease?

Research shows that vagus nerve stimulation (VNS) can enhance cognitive function in Alzheimer's patients over a year. Additionally, transcutaneous auricular vagus nerve stimulation (taVNS) has been found to improve brain connectivity in conditions similar to Alzheimer's, suggesting potential benefits for cognitive health. ^{1 2 3 4 5}

Is transcutaneous auricular vagus nerve stimulation (taVNS) safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe, with mild and temporary side effects like ear pain, headache, and tingling. There is no evidence of severe adverse effects directly caused by taVNS, making it a safe option for clinical use. ^{6 7 8 9 10}

How does the treatment of transcutaneous auricular vagus nerve stimulation (taVNS) for Alzheimer's disease differ from other treatments?

Transcutaneous auricular vagus nerve stimulation (taVNS) is unique because it is a non-invasive treatment that stimulates the vagus nerve through the skin of the ear, potentially enhancing cognitive function in Alzheimer's patients without the need for surgery or medication. This method is less expensive and more accessible compared to traditional invasive vagus nerve stimulation, which requires surgical implantation. ^{1 2 10 11 12}

What is the purpose of this trial?

This study will determine how noninvasive nerve stimulation affects human brain, stomach, and autonomic activity.

Research Team

Vitaly Napadow, PhD

Principal Investigator

Harvard University

Eligibility Criteria

This trial is for right-handed, healthy individuals without any neurological or psychiatric disorders, pain syndromes, or conditions that would make an fMRI brain scan unsafe.

Inclusion Criteria

You must be right-handed.

Exclusion Criteria

You have any problems related to your brain or mental health.

You have any type of pain condition.

You have a medical condition that prevents you from undergoing an fMRI brain scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 3 fMRI brain-gut scans with neuromodulation and physiological monitoring

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• active auricular tVNS
• inactive auricular tVNS

Trial Overview The study tests how active Transcutaneous Electrical Acupoint Stimulation (TEAS) affects the brain, stomach function, and autonomic nervous system activity in healthy subjects.

Participant Groups

Group I: Incongruent Experimental Treatment 1 Intervention

Participants receive briefings on expectations of stimulation effects on gastric motility inconsistent with the literature.

Group II: Congruent Experimental Treatment 1 Intervention

Participants receive briefings on expectations of stimulation effects on gastric motility consistent with the literature.

active auricular tVNS is already approved in European Union, United States for the following indications:

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Migraine
• Depression
• Chronic Pain
• Autoimmune Diseases

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Migraine
• Depression
• Chronic Pain

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

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]

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]

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]

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 vagus nerve stimulation (tVNS) was shown to alter brain connectivity in patients with mild cognitive impairment (MCI), suggesting it may positively impact cognitive functions related to Alzheimer's disease.

In a study of 50 MCI patients using resting state fMRI, tVNS led to changes in functional connectivity in brain regions associated with semantic and salience functions, indicating its potential as a noninvasive therapeutic intervention for improving brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment. Murphy, AJ., O'Neal, AG., Cohen, RA., 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]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

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]

Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive and less expensive alternative to invasive vagus nerve stimulation (VNS), which is used to treat conditions like epilepsy and depression, but requires further research to optimize stimulation sites and parameters.

tVNS has the potential to activate various brain areas and may be effective for a wide range of conditions, including medication-refractory epilepsy, depression, migraines, and more, suggesting it could become a standard treatment for enhancing autonomic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. Hilz, MJ.[2022]

A pilot study involving 37 patients with major depression showed that non-invasive auricular transcutaneous electric nerve stimulation (tVNS) resulted in a significant improvement in depression symptoms as measured by the Beck Depression Inventory, with an average score decrease of 12.6 points compared to 4.4 points in the sham group.

While the Hamilton Depression Rating Scale did not show significant changes, this study is the first to suggest an antidepressant effect of tVNS, indicating potential for further research despite limitations like small sample size and the need for more robust testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. Hein, E., Nowak, M., Kiess, O., et al.[2021]

References

1. United States 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. [2022]

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

Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. [2022]

3. China pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]

4. Turkey pubmed.ncbi.nlm.nih.gov

The effects of transcutaneous auricular vagus nerve stimulation on visual memory performance and fatigue. [2023]

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

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. [2023]

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

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]

12. Austria pubmed.ncbi.nlm.nih.gov

Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. [2021]