Ear Nerve Stimulation for Brain Bleed

Recruiting at 2 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether stimulating a nerve in the ear can aid recovery for individuals who have experienced a brain bleed, specifically a spontaneous subarachnoid hemorrhage (a type of bleeding in the space around the brain). The researchers aim to determine if this treatment, known as Auricular Vagus Nerve Stimulation, can reduce inflammation and enhance recovery. Participants will receive either the actual nerve stimulation or a sham (fake) treatment that feels the same but has no effect. This trial might suit those who have experienced a spontaneous subarachnoid hemorrhage and are not currently on chemotherapy, taking immunosuppressive drugs, or have a pacemaker. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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 prior data suggests that auricular vagus nerve stimulation is safe for brain bleed patients?

Research has shown that auricular vagus nerve stimulation (taVNS) is generally safe for people. A detailed review and analysis found this type of nerve stimulation both safe and practical. Another study focused on its safety for patients with a specific type of brain bleed called subarachnoid hemorrhage. This study found no negative effects on heart function, such as slowing heart rate or changes in heart rhythm. Overall, taVNS appears well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about auricular vagus nerve stimulation (VNS) for brain bleeds because it offers a novel, non-invasive approach that could potentially enhance recovery. Unlike standard treatments like surgery or medication that target the bleed directly, auricular VNS works by stimulating the vagus nerve via the ear, which may help reduce inflammation and promote brain healing. This technique is unique because it uses electrical impulses to tap into the body's natural healing processes, possibly leading to quicker and safer recovery outcomes.

What evidence suggests that auricular vagus nerve stimulation is effective for brain bleed?

Research has shown that stimulating a nerve in the ear, known as auricular vagus nerve stimulation, might aid recovery from certain types of brain bleeds. In this trial, participants will receive either auricular vagus nerve stimulation or a sham version of the treatment. Studies have found that this stimulation can support the brain's healing process after such injuries. It also reduces inflammation, which can be harmful after a brain bleed. Importantly, research has found this treatment to be safe, as it does not cause major side effects like heart problems. Therefore, auricular vagus nerve stimulation is considered a promising method to improve recovery after a brain bleed. ^{1 2 3 5 6}

Who Is on the Research Team?

Eric Leuthardt, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12278549/

Transcutaneous auricular vagus nerve stimulation enhances ... Most research on VNS has focused on chronic ischemic stroke, however, ischemic and hemorrhagic strokes have distinct pathophysiological ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06918964

NCT06918964 | TaVNS for Acute Intracerebral Hemorrhage This study aims to evaluate the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in patients with acute intracerebral ...

3. elifesciences.org elifesciences.org/reviewed-preprints/100088

The effect of transcutaneous auricular vagus nerve ... Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a ...

4. nature.com nature.com/articles/s41598-022-25864-1

Safety of transcutaneous auricular vagus nerve stimulation ... This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40691625/

Transcutaneous auricular vagus nerve stimulation ... Transcutaneous auricular vagus nerve stimulation enhances structural and functional remodeling in sensorimotor networks following intracerebral ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38633771/

The effect of transcutaneous auricular vagus nerve stimulation ... The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.