Ear Nerve Stimulation for Brain Bleed

Recruiting at 1 trial location

Overseen By Anna L Huguenard, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Anna Huguenard

Must not be taking: Immunosuppressives, Chemotherapy

Disqualifiers: Trauma-induced hemorrhage, Pacemaker, Bradycardia, 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: 1

Duration: 4 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following spontaneous subarachnoid hemorrhage.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking immunosuppressive medications.

What data supports the effectiveness of the treatment Auricular Vagus Nerve Stimulation for brain bleed?

Research shows that transcutaneous auricular vagus nerve stimulation (taVNS) has been effective in improving brain activity in patients with consciousness disorders and has shown antidepressant effects in patients with depression. This suggests that taVNS may have potential benefits for brain-related conditions, although more research is needed specifically for brain bleeds. ^{1 2 3 4 5}

Is ear nerve stimulation safe for humans?

Ear nerve stimulation, specifically transcutaneous auricular vagus nerve stimulation (taVNS), is generally considered safe for humans. Most studies report only mild and temporary side effects like ear pain, headache, and tingling, with no severe adverse events linked to the treatment. ^{4 6 7 8 9}

How is the treatment of auricular vagus nerve stimulation for brain bleed different from other treatments?

Auricular vagus nerve stimulation (taVNS) is unique because it is a non-invasive treatment that uses electrical currents applied to the ear to stimulate the vagus nerve, unlike traditional invasive methods that require surgery. This approach is less expensive, more accessible, and can modulate various brain and body functions, potentially offering a novel way to manage conditions like brain bleeds. ^{1 2 4 10 11}

Research Team

Eric Leuthardt, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for individuals who have experienced a spontaneous subarachnoid hemorrhage, which is bleeding in the space around the brain. It's not open to those with trauma-induced bleeding, anyone on chemotherapy or immunosuppressive medications, people with pacemakers, or patients who had very slow heart rates when admitted.

Inclusion Criteria

I have had a bleeding in the space around my brain.

Exclusion Criteria

I am on medication to suppress my immune system for another illness.

I am currently receiving chemotherapy.

I have bleeding in my brain caused by an injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either auricular vagal nerve stimulation or sham stimulation twice daily during hospital admission

4 weeks

Daily monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with functional scores assessed at discharge and follow-up visits

2 years

Regular follow-up visits

Treatment Details

Interventions

• Auricular Vagus Nerve Stimulation
• Sham Auricular Vagus Nerve Stimulation

Trial Overview The study tests auricular vagus nerve stimulation (VNS), a non-invasive treatment that involves stimulating a nerve in the ear to see if it can reduce inflammation and improve recovery after a spontaneous subarachnoid hemorrhage. Some participants will receive sham VNS as a comparison.

Participant Groups

Group I: Auricular VNS Stimulation Experimental Treatment 1 Intervention

Participants receive twice daily auricular vagal nerve stimulation

Group II: Sham Auricular VNS Stimulation Placebo Group 1 Intervention

Participants will have an auricular vagal nerve stimulator applied twice daily, without the stimulation applied

Auricular Vagus Nerve Stimulation is already approved in United States, European Union for the following indications:

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

• Epilepsy
• Depression
• Chronic pain
• Stroke rehabilitation

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

• Epilepsy
• Depression
• Chronic pain

Who Is Running the Clinical Trial?

Anna Huguenard

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

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]

In a study involving 26 subjects, simultaneous stimulation of the cymba and concha (CC) areas of the ear using extra-large electrodes was found to be the most effective for eliciting vagus somatosensory evoked potentials (VSEP), indicating strong neuromodulation effects.

The research demonstrated that the earlobe is not an effective target for taVNS, and using larger electrodes not only increased the amplitude of the response but also made the stimulation more comfortable for participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. de Gurtubay, IG., Bermejo, P., Lopez, M., et al.[2021]

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) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

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]

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) 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]

Noninvasive transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) significantly reduces spontaneous ventricular arrhythmias in beagle dogs after myocardial infarction, indicating its potential as an antiarrhythmic treatment.

AB-VNS enhances ventricular electrical stability and reduces ventricular interstitial fibrosis, although it does not improve overall cardiac function or reverse structural changes in the heart after 4 weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. Nasi-Er, BG., Wenhui, Z., HuaXin, S., et al.[2019]

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]

The auricular branch of the vagus nerve (ABVN), located in the ear, has potential for non-invasive electrical stimulation to improve heart function, offering a simpler alternative to traditional vagus nerve stimulation (VNS) that requires surgery.

This review highlights the growing interest and evidence supporting the use of ABVN stimulation as a cost-effective method for modulating cardiac activity, which could lead to new treatment options for heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. Murray, AR., Atkinson, L., Mahadi, MK., et al.[2018]

The study demonstrates that millimeter wave (MMW) stimulation can selectively activate the auricular branch of the vagus nerve (ABVN) without affecting nearby non-vagal nerves, as shown by significant increases in local field potential (LFP) power in the nucleus tractus solitarii (NTS) during targeted stimulation.

In contrast, non-vagal nerve stimulation resulted in decreased LFP power, indicating that MMW can effectively differentiate between vagal and non-vagal responses, paving the way for a new clinical treatment approach for conditions like depression and epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. Song, HY., Shin, DW., Jung, SM., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. [2021]

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

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

5. Austria pubmed.ncbi.nlm.nih.gov

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. [2019]

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

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

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

The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. [2022]