Clinical trial NCT04126408: Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage
Official title: Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Subarachnoid Hemorrhage, Aneurysmal
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2019-10-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Difference Between the Active and Sham Treatment Groups in Morphine Equivalence Dosage PER DAY
timeFrame: up to 14 days of admission
measure: Overall Difference in MED at 7 Days
timeFrame: baseline and 7 days
Secondary outcomes:
measure: The Difference Between the Active and Sham Treatment Groups in the Mean Daily Headache Intensity Pre and Post Stimulation
timeFrame: up to 14 days of admission
measure: The Difference in Device Related Heart Rate Change Before and After Stimulation
timeFrame: up to 14 days of admission
measure: Change in SBP Between Active and Sham Group
timeFrame: before and after stimulation, up to 14 days
Other outcomes:
Locations:
city: Manhasset
country: United States
facility: Northshore University Hospital
state: New York
Study officials:
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