Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage
Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage
This is a single site, randomized, sham-controlled, double blinded pilot study assessing the
 feasibility, safety, tolerability, and efficacy of non-invasive VNS (nVNS), gammaCore, in the
 treatment of headache in subarachnoid hemorrhage (SAH). 40 participants will be enrolled, 20
 in the active device arm and 20 in the sham arm. The primary efficacy outcome is the the
 difference between the active and sham treatment groups in morphine equivalence dosage.
This is a single site, randomized, sham-controlled, double-blind study assessing the
 feasibility, safety, tolerability, and efficacy of non-invasive VNS (nVNS) in the treatment
 of headache in subarachnoid hemorrhage (SAH). The hypothesis is that two-two minute
 noninvasive stimulations of the cervical branch of the Vagus nerve, every 5 hours, is
 efficacious in safely reducing headache intensity and frequency in patients with headache due
 to SAH, during the patient's intensive care unit (ICU) stay. After screening and obtaining
 informed consent, eligible patients diagnosed with SAH on head scans, admitted to the
 Neurosurgical Intensive Care Unit (NSCU) at Northshore University Hospital will be randomized
 to either the treatment (stimulation of the cervical branch of the Vagus nerve) or sham
 (inactive stimulation) group. Pain intensity will be evaluated every 4 hours. Non-invasive
 stimulation will be performed every 5 hours. Device related adverse events, mean headache
 intensity, and mean and peak morphine equivalence dosage during the study period will be
 compared between the VNS group and the sham group.

 The primary objective of this study is to examine the safety and effectiveness of nVNS as a
 treatment for headache in subarachnoid hemorrhage (SAH).

 The primary safety endpoint for this study is the incidence of device related serious adverse
 events.

 The primary outcome measurements for effectiveness is the difference between the active and
 sham treatment groups in morphine equivalence dosage

 Secondary endpoints include descriptive comparisons between the active and sham treatment
 groups in:

 -  The difference between the active and sham treatment groups in the mean daily headache
 intensity

 -  The difference between total overall morphine equivalence dosage between the active and
 sham group per subject during study

 -  Opiate related adverse events (such as urinary retention, constipation, sedation,
 respiratory depression, nausea, vomiting and pruritis)

 -  The difference in CSF and blood inflammatory markers before and after VNS

 -  Difference in vessel diameter during angiogram for cerebral vasospasm before and after
 VNS

 Study period is 14 days starting 24-72 hours post successful treatment of the aneurysm and
 extubation.
Inclusion Criteria:

 -  Established signed and dated informed consent form

 -  CT of the head revealing blood in the subarachnoid space

 -  Subject is male or female, 18 to 80 years of age

 -  Subject alert to be able to verbalize pain level. If alertness improves after
 placement of an external ventricular drain, or once extubated, and the patient becomes
 alert , the patient will be enrolled

 -  Subject reports pain of > =7 on 10 Point Pain numeric rating scale

 -  Female of reproductive age must have a negative pregnancy test (Urine or blood test)

 Exclusion Criteria:

 -  Use of any concomitant electrostimulation devices (Pacemaker, defibrillator, deep
 brain stimulation.)

 -  Unsecured aneurysm defined as aneurysm that has not been surgically or endovascularly
 treated.

 -  Previous carotid surgeries or known history of carotid artery disease

 -  Screws, metals or device in the neck

 -  History of secondary or tertiary heart blocks, ventricular tachycardia,
 Supra-Ventricular Tachycardia (including atrial fibrillation)

 -  Alcoholics (CAGE scale of 2 or greater). If patients are on Clinical Institute
 Withdrawal Assessment for Alcohol (CIWA) protocol for alcohol withdrawal, the patient
 will be excluded from the study.

 -  Drug addicts or chronic opioid users confirmed by history or with urine toxicology
 showing opiates or cocaine

 -  small traumatic SAH