Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following intracerebral hemorrhage.
Vagal nerve stimulation (VNS) has been studied as a novel method of reducing inflammation, and it has been successfully used in animal models of inflammatory conditions. The purpose of the proposed study is to determine if transcutaneous auricular VNS will impact inflammatory markers in the blood and cerebrospinal fluid (CSF) in patients with intracerebral hemorrhage, and how it impacts their clinical course and outcomes.
This study will involve randomizing patients to stimulation with VNS, or sham stimulation. Blood and CSF will be collected on admission, and serially throughout the patient's admission. Clinical events tracked during the hospital stay include the development of peri-hematomal edema, interventions for edema (medical or surgical), and intensive care unit and hospital stay. Outcomes following admission will include functional scores at discharge, and at follow-up visits for up to 2 years after discharge. No additional appointments will be made specially for the research study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Auricular VNS Stimulation | Experimental | Participants receive twice daily auricular vagal nerve stimulation |
|
| Sham Auricular VNS Stimulation | Sham Comparator | Participants will have an auricular vagal nerve stimulator placed in their ear twice daily, without the stimulation applied |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Auricular Vagus Nerve Stimulation | Device | Transcutaneous auricular vagal nerve stimulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in the inflammatory marker IL-6 in plasma | Blood samples collected on days 1, 4, 7, 10, and 14 (Day 1 serves as baseline, prior to first treatment). Inflammatory markers will be reported in pg/mL. | 14 days |
| Growth of perihematomal edema | Change in edema extension distance (baseline vs. peak) will be compared between groups, via quantitative assessment of serial computed tomography (CT) scans obtained on day 1, 4, 7, 10, and 14 (Day 1 serves as baseline, prior to first treatment). | 14 days |
| Neurological worsening | Occurrence of clinical deterioration due to edema by criteria of 1) a reduction in GCS by 2 points or greater that persists for at least one hour, 2) worsening focal neurological deficits (NIHSS increase by at least 4 points), excluding other causes, or 3) need for surgical intervention or medical treatments for edema (osmotic therapies). | Through hospital admission, average 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Change in additional inflammatory markers in plasma | Blood samples collected on days 1, 4, 7, 10, and 14 to evaluate for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17a, GM-CSF, IFN gamma, and TNF-α. Inflammatory markers will be reported in pg/mL. | 14 days |
| Change in inflammatory markers in cerebrospinal fluid |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Raj Dhar, MD | Contact | 314-362 2999 | dharr@wustl.edu |
| Name | Affiliation | Role |
|---|---|---|
| Eric Leuthardt, MD MBA | Washington University School of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38746275 | Background | Huguenard AL, Tan G, Rivet DJ, Gao F, Johnson GW, Adamek M, Coxon AT, Kummer TT, Osbun JW, Vellimana AK, Limbrick DD, Zipfel GJ, Brunner P, Leuthardt EC. Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial. medRxiv [Preprint]. 2024 May 1:2024.04.29.24306598. doi: 10.1101/2024.04.29.24306598. | |
| 39178291 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| D010335 | Pathologic Processes |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002318 | Cardiovascular Diseases |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
Participants are assigned to either stimulation or sham stimulation arms
Not provided
Not provided
All participants will be fitted with an auricular stimulator, but blinded to whether they are receiving stimulation or not. Outcome scores will be assessed and recorded by clinicians blinded to treatment arm.
| Sham Auricular Vagus nerve Stimulation | Device | Transcutaneous auricular vagal nerve ear clip applied without current |
|
Cerebrospinal fluid samples collected on days 1, 4, 7, 10, and 14 to evaluate for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17a, GM-CSF, IFN gamma, and TNF-α. Inflammatory markers will be reported in pg/mL. |
| 14 days |
| Relative perihematomal edema | Relative perihematomal edema volume, the ratio of perihematoma volume to intracerebral hematoma volume | 14 days |
| Neurological outcome | Modified Rankin Scale for Neurological Disability (minimum score 0, maximum score 6, better outcomes have lower scores) | 2 years |
| Hospital length of stay | Total length of stay in the hospital, and in the intensive care unit | Through hospital admission, average 14 days |
| Huguenard A, Tan G, Johnson G, Adamek M, Coxon A, Kummer T, Osbun J, Vellimana A, Limbrick D Jr, Zipfel G, Brunner P, Leuthardt E. Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial. PLoS One. 2024 Aug 23;19(8):e0301154. doi: 10.1371/journal.pone.0301154. eCollection 2024. |
| 39786346 | Background | Tan G, Huguenard AL, Donovan KM, Demarest P, Liu X, Li Z, Adamek M, Lavine K, Vellimana AK, Kummer TT, Osbun JW, Zipfel GJ, Brunner P, Leuthardt EC. The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial. Elife. 2025 Jan 9;13:RP100088. doi: 10.7554/eLife.100088. |