Clinical trial NCT05103566: Safety, Feasibility, and Efficacy of Non-invasive Vagus Nerve Stimulation (nVNS) in the Treatment of Aneurysmal Subarachnoid Hemorrhage
Official title: STORM: Safety, Feasibility, and Efficacy of Non-invasive Vagus Nerve Stimulation (nVNS) in the Treatment of Aneurysmal Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Keywords: Aneurysm
Hemorrhage
Intracranial Hemorrhages
Cerebrovascular Disorders
Intracranial Aneurysm
Vascular Diseases
Aneurysm, Brain
Brain Diseases
Central Nervous System Diseases
Aneurysm, Ruptured
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: ElectroCore INC
First posted: 2021-11-02
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-site, single-arm, open-label pilot study assessing the safety, feasibility, and efficacy of non-invasive vagus nerve stimulation (nVNS), gammaCore, for the acute treatment of aneurysmal subarachnoid hemorrhage (SAH) subjects in a neurocritical care setting. 25 patients will be enrolled, all treated with an active device. The primary efficacy outcomes are reduced aneurysm rupture rate, reduced seizure and seizure-spectrum activity, minimized hemorrhage grades, and increased survival.

Detailed description: This is a single-site, single-arm, open-label pilot study assessing the safety, feasibility, and efficacy of non-invasive vagus nerve stimulation (nVNS), gammaCore, for the acute treatment of aneurysmal subarachnoid hemorrhage (SAH). The hypothesis is that two 2-minute non-invasive stimulations of the cervical branch of the vagus nerve with nVNS, 3 times daily (TID), is a safe, practical, and potentially effective treatment after SAH in the neurocritical care setting. After diagnosis and surgical repair of the SAH, patients admitted to the Neuroscience Intensive Care Unit (NeuroICU) at Massachusetts General Hospital (MGH) will be screened for eligibility. Upon providing informed consent, eligible patients will be enrolled, begin the treatment protocol, and will be monitored. Data collection will be completed using automated systems, electronic reports, and manual collection before, during, and after nVNS.

The primary objective is to examine the safety, feasibility, and possible efficacy of nVNS as a treatment after aneurysmal subarachnoid hemorrhage (SAH).

Safety will be assessed by the incidence of severe adverse device events (SADEs) following nVNS.

Feasibility of the nVNS implementation will be evaluated by the ability to deliver \>85% of doses per protocol, report of minimal interference with current standard of care treatments and procedures in in the NeuroICU, and beginning of treatment within 72 hours of presumed aneurysm rupture.

Efficacy of nVNS will be explored using the following assessments:

* subject disability measured using mRS at 10 days (or discharge) and 90 days after SAH
* effects on EEG, TCD, and ICP before, during, and after nVNS
* DCI/ischemic stroke detected by CT scans and/or angiography
* HR (heart rate), HR variability, and BP before, during, and after nVNS

The study period starts within 72 hours of presumed aneurysm rupture and ends at 10 days or discharge, if sooner.

The PI and co-investigators will conduct safety monitoring of this small, single-site, low-risk pilot study on a continuous basis, ensuring adherence to the Mass General Brigham (MGB) Institutional Review Board (IRB) guidelines accordingly.

Eligibility criteria: Inclusion Criteria:

* Male or female, 18-85 years of age
* Ruptured aneurysmal SAH confirmed by angiography and repaired by neurosurgical clipping or endovascular occlusion (coiling)
* Modified Glasgow Coma Scale (mGCS) score ≥ 10 and Hunt Hess 1-4 within 72 hours of presumed aneurysm rupture
* Enrollment and initiation of nVNS treatment must occur within 72 hours of presumed aneurysm rupture
* Provide a legally obtained informed consent form from the participant or the legally authorized representative (LAR); telephonic consent is acceptable
* Female participants of reproductive age must have a negative pregnancy test result (urine or blood)

Exclusion Criteria:

* Use of any concomitant electrostimulation device, including a pacemaker, defibrillator, or deep brain stimulator
* No plan to secure aneurysm, defined as aneurysm that has not been surgically or endovascularly treated
* Previous neck dissection or radiation
* History of carotid artery disease or carotid surgery/dissection
* History of secondary or tertiary heart blocks, ventricular tachycardia, or supraventricular tachycardia (SVT; including atrial fibrillation)
* Screws, metals, or devices in the neck
* Currently participating in an investigational drug or device clinical trial with potential to confound data collection

Primary outcomes:
measure: The presentation of severe adverse device events (SADEs) within 30 minutes of nVNS first treatment dose.
timeFrame: up to 10 days post-rupture
Secondary outcomes:
measure: The feasibility of nVNS in SAH subjects in the critical care setting.
timeFrame: up to 10 days post-rupture
measure: The frequency of alarm triggers peri-nVNS.
timeFrame: up to 10 days post-rupture
measure: The measure of subject disability using a modified Rankin Score at baseline, intervention completion (10 days), and follow up (90 days).
timeFrame: at 10 days and 90 days post-rupture
measure: The rate of established predictors of delayed cerebral ischemia (DCI) and outcome.
timeFrame: up to 10 days post-rupture
measure: The occurrence of ischemic complications.
timeFrame: up to 10 days post-rupture
measure: The self-reported assessment for the quality of life of patients with neurological disorders at follow up (90 days).
timeFrame: at 90 days post-rupture
measure: The self-reported assessment for physical, mental, and social health at follow up (90 days).
timeFrame: at 90 days post-rupture
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Aman B Patel, MD
role: PRINCIPAL_INVESTIGATOR
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