Ear Nerve Stimulation for Brain Bleed
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Anna Huguenard
Must not be taking: Immunosuppressives, Chemotherapy
Disqualifiers: Trauma-induced hemorrhage, Pacemaker, Bradycardia, others
No Placebo Group
Approved in 2 Jurisdictions
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.
12345Is 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.
46789How 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.
1241011Eligibility 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.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Auricular VNS StimulationExperimental Treatment1 Intervention
Participants receive twice daily auricular vagal nerve stimulation
Group II: Sham Auricular VNS StimulationPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Washington University School of MedicineSt. Louis, MO
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Anna HuguenardLead Sponsor
References
Transcutaneous vagus nerve stimulation - A brief introduction and overview. [2022]Invasive cervical vagus nerve stimulation (VNS) is approved for the treatment of epilepsies, depression, obesity, and for stroke-rehabilitation. The procedure requires surgery, has side-effects, is expensive and not readily available. Consequently, transcutaneous VNS (tVNS) has been developed 20 years ago as non-invasive, less expensive, and easily applicable alternative. Since the vagus nerve reaches the skin at the outer acoustic canal and ear, and reflex-responses such as the ear-cough-reflex or the auriculo-cardiac reflex have been observed upon auricular stimulation, the ear seems well suited for tVNS. However, several sensory nerves with variable fiber-density and significant overlap innervate the outer ear: the auricular branch of the vagus nerve (ABVN), the auriculotemporal nerve, greater auricular nerve, and to some extent the lesser occipital nerve. VNS requires activation of Aβ-fibers which are far less present in the ABVN than the cervical vagus nerve. Thus, optimal stimulation sites and parameters, and tVNS-algorithms need to be further explored. Unravelling central pathways and structures that mediate tVNS-effects is another challenge. tVNS impulses reach the nucleus of the solitary tract and activate the locus-coeruleus-norepinephrine system. However, many more brain areas are activated or deactivated upon VNS, including structures of the central autonomic network and the limbic system. Still, the realm of therapeutic tVNS applications grows rapidly and includes medication-refractory epilepsies, depressive mood disorders, headaches including migraine, pain, heart failure, gastrointestinal inflammatory diseases and many more. tVNS might become a standard tool to enhance autonomic balance and function in various autonomic, neurological, psychiatric, rheumatologic, as well as other diseases.
Evaluation of different vagus nerve stimulation anatomical targets in the ear by vagus evoked potential responses. [2021]Electrical auricular vagus nerve stimulation (taVNS) is an emerging therapy. Stimuli are transported to brainstem nuclei, whereby its multiple projections reach to many subcortical and cortical areas, thus allowing the neuromodulation of several systemic physiological processes. We aim to define the best auricular target for taVNS through vagus somatosensory evoked potential (VSEP) elicited stimulating different auricular areas with different electrode sizes.
Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study. [2023]To evaluate the clinical effect of transcutaneous auricular vagus nerve nerve stimulation (taVNS) on disorders of consciousness (DOC) patients with Coma Recovery Scale-Revised (CRS-R) and cerebral cortex activity by electroencephalogram (EEG) detection.
High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]Transcutaneous auricular Vagus Nerve Stimulation (taVNS) applies low-intensity electrical current to the ear with the intention of activating the auricular branch of the Vagus nerve. The sensitivity and selectivity of stimulation applied to the ear depends on current flow pattern produced by a given electrode montage (size and placement).
Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. [2021]Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes. Recently, a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed. In healthy subjects, a prominent fMRI BOLD signal deactivation in the limbic system was found. The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time. A total of 37 patients suffering from major depression were included in two randomized sham controlled add-on studies. Patients were stimulated five times a week on a daily basis for the duration of 2 weeks. On days 0 and 14, the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were assessed. In contrast to sham-treated patients, electrically stimulated persons showed a significantly better outcome in the BDI. Mean decrease in the active treatment group was 12.6 (SD 6.0) points compared to 4.4 (SD 9.9) points in the sham group. HAMD score did not change significantly in the two groups. An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown for the first time in this controlled pilot study. Regarding the limitations of psychometric testing, the risk of unblinding for technical reasons, and the small sample size, further studies are necessary to confirm the present results and verify the practicability of tVNS in clinical fields.
Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]As an emerging neuromodulation therapy, transcutaneous auricular vagus nerve stimulation (taVNS) has been proven to be safe and effective for epilepsy, major depressive disorders, insomnia, glucose metabolic disorders, pain, stroke, post stroke rehabilitation, anxiety, fear, cognitive impairment, cardiovascular disorders, tinnitus, Prader-Willi Syndrome, and COVID-19.
Vagus nerve stimulation reduces ventricular arrhythmias and increases ventricular electrical stability. [2019]Transcutaneous stimulation of the auricular branch of the vagus nerve (AB-VNS) is a potentially noninvasive, inexpensive, and safe approach for vagus nerve stimulation that suppresses the induction and duration of atrial fibrillation and reduces sympathetic nerve outflow in healthy humans. Researchers have not determined whether AB-VNS affects ventricular arrhythmias.
Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]Vagus nerve stimulation (VNS) is effective in refractory epilepsy and depression and is being investigated in heart failure, headache, gastric motility disorders and asthma. The first VNS device required surgical implantation of electrodes and a stimulator. Adverse events (AEs) are generally associated with implantation or continuous on-off stimulation. Infection is the most serious implantation-associated AE. Bradycardia and asystole have also been described during implantation, as has vocal cord paresis, which can last up to 6 months and depends on surgical skill and experience. The most frequent stimulation-associated AEs include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis and pain, which may require a decrease in stimulation strength or intermittent or permanent device deactivation. Newer non-invasive VNS delivery systems do not require surgery and permit patient-administered stimulation on demand. These non-invasive VNS systems improve the safety and tolerability of VNS, making it more accessible and facilitating further investigations across a wider range of uses.
The strange case of the ear and the heart: The auricular vagus nerve and its influence on cardiac control. [2018]The human ear seems an unlikely candidate for therapies aimed at improving cardiac function, but the ear and the heart share a common connection: the vagus nerve. In recent years there has been increasing interest in the auricular branch of the vagus nerve (ABVN), a unique cutaneous subdivision of the vagus distributed to the external ear. Non-invasive electrical stimulation of this nerve through the skin may offer a simple, cost-effective alternative to the established method of vagus nerve stimulation (VNS), which requires a surgical procedure and has generated mixed results in a number of clinical trials for heart failure. This review discusses the available evidence in support of modulating cardiac activity using this strange auricular nerve.
Feasibility study on transcutaneous auricular vagus nerve stimulation using millimeter waves. [2022]Objective. Electrical stimulation of the auricular vagus nerve is a non-invasive neuromodulation technique that has been used for various conditions, including depression, epilepsy, headaches, and cerebral ischemia. However, unwanted non-vagal nerve stimulations can occur because of diffused stimulations. The objective of this study is to develop a region-specific non-invasive vagus nerve stimulation (VNS) technique using the millimeter wave (MMW) as a stimulus for the auricular branch of the vagus nerve (ABVN).Approach. A numerical simulation was conducted to ascertain whether the MMW could excite the ABVN in the human outer-ear with a millimeter-scale spatial resolution. Additionally, MMW-induced neuronal responses in seven mice were evaluated. Transcutaneous auricular VNS (ta-VNS) was applied to the cymba conchae innervated by the AVBN using a 60-GHz continuous wave (CW). As a control, the auricle's exterior margin was stimulated and referred to as transcutaneous auricular non-vagus nerve stimulation (ta-nonVNS). During stimulation, the local field potential (LFP) in the nucleus tractus solitarii (NTS), an afferent vagal projection site, was recorded simultaneously.Main results. The ta-VNS with a stimulus level of 13 dBm showed a significant increase in the LFP power in the NTS. The mean increases in power (n = 7) in the gamma high and gamma very high bands were 8.6 ± 2.0% and 18.2 ± 5.9%, respectively. However, the ta-nonVNS with a stimulus level of 13 dBm showed a significant decrease in the LFP power in the NTS. The mean decreases in power in the beta and gamma low bands were 11.0 ± 4.4% and 10.8 ± 2.8%, respectively. These findings suggested that MMW stimulation clearly induced a different response according to the presence of ABVN.Significance. Selective auricular VNS is feasible using the MMW. This study provides the basis for the development of a new clinical treatment option using the stimulation of the ta-VNS with a square millimeter spatial resolution.