Auricular VNS Following Subarachnoid Hemorrhage

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

Detailed Description
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Vagal nerve stimulation (VNS) has been studied in several inflammatory conditions, and has been implemented in animal models of subarachnoid hemorrhage (SAH) with promising results. The purpose of the proposed study is to determine how applying auricular VNS in patients presenting with spontaneous SAH impacts their expression of inflammatory markers in their blood and cerebrospinal fluid (CSF), 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 development of cerebral vasospasm, need for CSF diversion via a shunt, stress-induced cardiomyopathy, and development of stroke or global cerebral ischemia. Outcomes following admission will include functional scores at discharge, and at follow-up visits for up to 2 years after discharge.

Official Title
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Transcutaneous Auricular Vagus Nerve Stimulation Following Spontaneous Subarachnoid Hemorrhage

Conditions
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Subarachnoid Hemorrhage

Intervention / Treatment
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* Device: Auricular Vagus Nerve Stimulation
* Device: Sham Auricular Vagus nerve Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spontaneous subarachnoid hemorrhage Exclusion Criteria: Trauma-induced subarachnoid hemorrhage Ongoing chemotherapy Taking immunosuppressive medications for other medical illnesses Presence of a pacemaker Prolonged bradycardia at time of admission

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are assigned to either stimulation or sham stimulation arms
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Auricular VNS Stimulation<br>Participants receive twice daily auricular vagal nerve stimulation | Device: Auricular Vagus Nerve Stimulation<br>* Transcutaneous auricular vagal nerve stimulation<br>|
| Sham Comparator: Sham Auricular VNS Stimulation<br>Participants will have an auricular vagal nerve stimulator applied twice daily, without the stimulation applied | Device: Sham Auricular Vagus nerve Stimulation<br>* Transcutaneous auricular vagal nerve ear clip applied without current<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers in the serum on admission | IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, TNF alpha from blood draws | On hospital day 1 | 
| Change in inflammatory markers in the serum | IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, TNF alpha from blood draws | Through hospital admission, average of 4 weeks | 
| Inflammatory markers in the CSF on admission | IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, TNF alpha from cerebrospinal fluid | On hospital day 1 | 
| Change in inflammatory markers in the CSF on admission | IL-12, GM-CSF, IFN gamma, IL-1b, IL-10, IL-13, IL-17A, IL-2, IL-4, IL-5, IL-6, IL-8, TNF alpha from cerebrospinal fluid | Through hospital admission, average of 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral vasospasm | Presence of vasospasm based on any of the following criteria: 1) Radiographic evidence of vasospasm on CT angiogram or catheter angiogram, 2) Need for blood pressure augmentation or hypervolemia, 3) Need for intraarterial or intrathecal vasodilator, 4) Need for angioplasty | Through hospital admission, average of 4 weeks | 
| Hydrocephalus | Presence of hydrocephalus based on any of the following criteria: 1) Need for temporary CSF diversion via an external ventricular drain, 2) Need for permanent CSF diversion via a ventricular shunt | Through hospital admission, average of 4 weeks | 
| Stressed-induced cardiomyopathy | Presence of stressed-induced cardiomyopathy based on any of the following criteria: 1) New troponin elevation, 2) New EKG changes (specifically ST segment elevation, ST segment depression, left bundle branch block, prolonged QT interval), 3) New findings of cardiomyopathy on echocardiogram | Through hospital admission, average of 4 weeks | 
| Cerebral ischemia | Presence of cerebral ischemia based on the following criteria: Radiographic evidence of a new infarct or stroke | Through hospital admission, average of 4 weeks | 
| Clinical outcome | Modified Rankin Scale for Neurological Disability (minimum score 0, maximum score 6, better outcomes have lower scores) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vagal nerve stimulation