Auricular Vagus Nerve Stimulation for Stroke

Recruiting at 1 trial location

Overseen By Raj Dhar, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Cancer therapy, Bradycardia, Imminent death, others

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

Compensation: Varies

Number of Visits: 2

Duration: 14 days

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a non-invasive treatment, auricular vagus nerve stimulation, can aid recovery after a stroke caused by brain bleeding. The goal is to determine if this treatment reduces inflammation and improves recovery outcomes. Participants will receive either actual stimulation or a sham (inactive) treatment for comparison. The trial seeks adults who have experienced a spontaneous brain bleed (intracerebral hemorrhage) and are treated at Barnes Jewish Hospital. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance future stroke recovery treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What prior data suggests that auricular vagus nerve stimulation is safe for stroke patients?

Research has shown that stimulating the vagus nerve in the ear is generally safe. Most people experience only mild and short-lived side effects, and some studies found no side effects at all. This indicates that most people tolerate the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about auricular vagus nerve stimulation (VNS) for stroke recovery because it offers a non-invasive approach to therapy. Unlike standard treatments such as medication and physical therapy, auricular VNS uses electrical stimulation of the vagus nerve via the ear to potentially enhance brain recovery and improve motor function. This method leverages the body's own nervous system to aid in healing, which could lead to faster and more effective rehabilitation outcomes for stroke patients.

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

Research has shown that stimulating the vagus nerve in the ear (auricular VNS) might aid stroke recovery. In this trial, participants will receive either auricular VNS stimulation or a sham version without stimulation. Studies have found that auricular VNS can improve movement, particularly in the arms, by about 7 points on a movement ability scale. In animal studies, VNS reduced the size of the area affected by the stroke. It also appears to enhance emotional and sensory functions when combined with regular rehabilitation. These findings suggest that VNS could be a promising method to boost recovery after a stroke. ^{1 2 5 6 7}

Who Is on the Research Team?

Eric Leuthardt, MD MBA

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with a spontaneous stroke in the upper part of their brain. They must be treated at Barnes Jewish Hospital within 48 hours of the stroke and not have cancer treatment or planned surgery, except ventriculostomy. It's not for those under 18, with very large or small strokes, traumatic causes, extremely low responsiveness (GCS of 3), unreactive pupils, or very slow heart rates.

Inclusion Criteria

I had a stroke caused by bleeding in my brain and was treated at Barnes Jewish Hospital.

Exclusion Criteria

My bleeding is located in the lower part of my brain.

My brain bleed is thought to be caused by an injury.

Patients with ICH volume greater than 60 ml or less than 10 ml

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either auricular vagal nerve stimulation or sham stimulation twice daily

14 days

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

Follow-up visits up to 2 years post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Auricular Vagus Nerve Stimulation
• Sham Auricular Vagus nerve Stimulation

Trial Overview The study tests if auricular vagus nerve stimulation (a non-invasive ear treatment) can reduce inflammation and improve recovery after an upper-brain stroke. Participants will either receive this stimulation or a sham (fake) version to compare effects.

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 placed in their ear twice daily, without the stimulation applied

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

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]

In a pilot study involving 40 acute stroke patients, transcutaneous auricular electrical vagus nerve stimulation (ta-VNS) significantly improved swallowing function compared to a sham treatment, with benefits observed immediately after treatment and lasting for at least 4 weeks.

The study found no serious adverse events associated with ta-VNS, indicating it is a safe and noninvasive option for treating dysphagia in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcutaneous auricular vagus nerve stimulation on post-stroke dysphagia. Wang, Y., He, Y., Jiang, L., et al.[2023]

In a review of 111 patients who received vagus nerve stimulation (VNS) for refractory epilepsy, three cases of intraoperative bradycardia were observed during device testing, but no adverse cardiac events occurred postoperatively.

Despite the initial bradycardia during testing, all three patients experienced reduced seizure frequency after starting VNS therapy, indicating that VNS is safe and effective for managing epilepsy even when bradycardia is noted during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac responses of vagus nerve stimulation: intraoperative bradycardia and subsequent chronic stimulation. Ardesch, JJ., Buschman, HP., van der Burgh, PH., et al.[2022]

In a double-blinded randomized controlled trial with 60 acute stroke patients, transcutaneous auricular vagus nerve stimulation (ta-VNS) combined with conventional rehabilitation significantly improved recovery of motor, sensory, and emotional functions compared to sham treatment.

The study found no significant side effects from ta-VNS, indicating that it is a safe and effective noninvasive treatment option for patients recovering from acute ischemic or hemorrhagic strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients. Li, JN., Xie, CC., Li, CQ., et al.[2022]

Vagus nerve stimulation (VNS) combined with rehabilitation was found to be safe and feasible for improving arm function in stroke patients, with all participants completing the therapy despite some serious adverse events related to surgery.

At 90 days post-therapy, patients receiving active VNS showed a significant improvement in upper limb function compared to the control group, with an 88% clinically meaningful response rate, suggesting that VNS may enhance rehabilitation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation Paired With Upper Limb Rehabilitation After Chronic Stroke. Kimberley, TJ., Pierce, D., Prudente, CN., 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]

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-invasive treatment that can effectively improve motor function in patients who have experienced a stroke.

This review highlights the importance of stimulation parameters and timing, as well as the development of new devices, to enhance the application of taVNS in rehabilitating upper limb motor dysfunction after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation. Shi, X., Zhao, J., Xu, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improved upper limb motor function in 21 subacute ischemic stroke patients compared to a sham treatment, as measured by the Fugl-Meyer assessment and other functional tests after 15 days of intervention.

The study found taVNS to be safe, with only one reported case of skin redness, indicating it may be a beneficial and low-risk option for enhancing recovery in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and Safety of Transcutaneous Auricular Vagus Nerve Stimulation on Recovery of Upper Limb Motor Function in Subacute Ischemic Stroke Patients: A Randomized Pilot Study. Wu, D., Ma, J., Zhang, L., et al.[2021]

Auricular vagus nerve stimulation (aVNS) effectively reduces infarct volume in rats after transient focal ischemia, showing a significant decrease from 44.20% in controls to 31.65% in treated animals, indicating its potential as a neuroprotective treatment.

The stimulation activates specific brain regions associated with the vagus nerve, leading to improved neurological outcomes, suggesting that aVNS could be a non-invasive alternative for stroke treatment in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation of the vagus nerve dermatome in the external ear is protective in rat cerebral ischemia. Ay, I., Napadow, V., Ay, H.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38452937/

Transcutaneous auricular vagus nerve stimulation for post- ... Results: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements ...

2. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.043414

tVNS in Stroke: A Narrative Review on the Current State ... Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as a tool to reduce infarct size in animal models of hyperacute stroke.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1052305722000878

Effect of Combined Vagus Nerve Stimulation on Recovery ... The study suggested that VNS combined with rehabilitation therapies offers improving benefits, tolerance and prospect for UE recovery after stroke. Ta-VNS ...

4. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.889953/full

Efficacy and Safety of Vagus Nerve Stimulation on Upper ... VNS together with physical therapy increases upper limb motor recovery of stroke patients by an average of 7 points in the Fugl-Meyer scale, ...

5. journals.lww.com journals.lww.com/nrronline/fulltext/2022/08000/efficacy_and_safety_of_transcutaneous_auricular.37.aspx

Efficacy and safety of transcutaneous auricular vagus ... ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses.

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

Safety of transcutaneous auricular vagus nerve stimulation ... Although the general impression is that taVNS is a safe technique with only mild and transient adverse effects (AEs), human data on safety and ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306452225003306

Review Vagus nerve stimulation in various stages of stroke ... This review highlights the mechanistic underpinnings and clinical outcomes of VNS across stroke phases, while also emphasizing the current ...