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Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage (VANQUISH)

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ClinicalTrials.gov Identifier: NCT04126408
Recruitment Status : Recruiting
First Posted : October 15, 2019
Last Update Posted : February 17, 2021
Sponsor:
Information provided by (Responsible Party):
Tania Rebeiz, Northwell Health

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.

Condition or disease Intervention/treatment Phase
Subarachnoid Hemorrhage, Aneurysmal Device: gammaCore Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Non-invasive Vagus Nerve Stimulation in the Treatment of Headache in Subarachnoid Hemorrhage
Actual Study Start Date : January 13, 2020
Estimated Primary Completion Date : January 30, 2022
Estimated Study Completion Date : May 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Headache

Arm Intervention/treatment
Sham Comparator: Sham arm
gammaCore sham device which will not provide stimulation of the vagus nerve
Device: gammaCore
The intervention consists of a transcutaneous non-invasive stimulation of the cervical branch of the vagus nerve (nVNS) using gammaCore, an FDA approved device for the treatment of migraine and cluster headache. This will be compared to the sham device, which is the same device which will not provide stimulation to the nerve. Stimulation frequency will be identical to the frequency used in previous nVNS studies for the treatment of migraine headache.

Active Comparator: Treatment group
Active gammaCore device that supplies non-invasive stimulation of the cervical branch of the Vagus nerve
Device: gammaCore
The intervention consists of a transcutaneous non-invasive stimulation of the cervical branch of the vagus nerve (nVNS) using gammaCore, an FDA approved device for the treatment of migraine and cluster headache. This will be compared to the sham device, which is the same device which will not provide stimulation to the nerve. Stimulation frequency will be identical to the frequency used in previous nVNS studies for the treatment of migraine headache.




Primary Outcome Measures :
  1. The difference between the active and sham treatment groups in morphine equivalence dosage [ Time Frame: up to 14 days of admission ]
    Daily morphine equivalence dosage will be calculated and compared between the active and Sham group


Secondary Outcome Measures :
  1. The difference between the active and sham treatment groups in the mean daily headache intensity [ Time Frame: up to 14 days of admission ]
    Headache intensity is measured every 4 hours per standard of care. The pain intensity is reported using a 0 to 10 numeric rating scale, o being no pain, and 10 being severe pain. The mean daily headache intensity will be measured and compared between the active and sham group

  2. The difference between total overall morphine equivalence dosage between the active and sham group per subject during study [ Time Frame: up to 14 days of admission ]
  3. The difference in opiate related adverse events [ Time Frame: up to 14 days of admission ]
    The rate of opiate related adverse events such as urinary retention, constipation, respiratory depression, central nervous system depression will be compared between the 2 groups

  4. The difference in CSF and blood inflammatory markers before and after VNS. When possible, if there is an EVD, 2 cc of CSF and 5 cc of blood will be analyzed for inflammatory markers. [ Time Frame: up to 14 dats of admission ]
    CSF and blood samples will be collected before the first stimulation and 24 hours after stimulation and during the vasospasm period. The blood and CSF will be analyzed for Interleukins, TNF, blood brain permeability markers like MMP. Immunologic investigations include but not limited to, measurement of inflammatory protein levels, RNA sequencing of leukocyte and stimulation assays.

  5. The difference in CSF and blood Blood brain permeability markers before and after VNS. When possible, if there is an EVD, 2 cc of CSF and 5 cc of blood will be analyzed for inflammatory markers. [ Time Frame: up to 14 dats of admission ]
    CSF and blood samples will be collected before the first stimulation and 24 hours after stimulation and during the vasospasm period. The blood and CSF will be analyzed for Blood brain permeability markers like MMP

  6. The difference in vessel diameter during cerebral vasospasm during cerebral angiography before and after VNS [ Time Frame: up to 14 dats of admission ]
    VNS will be delivered during angiography to evaluate the effect on cerebral vasospasm



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04126408


Contacts
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Contact: tania rebeiz, MD 9176734908 trebeiz@northwell.edu
Contact: Betsy Moclair, RN 5162537753 bmoclaire@northwell.edu

Locations
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United States, New York
Northshore University Hospital Recruiting
Manhasset, New York, United States, 11030
Contact: tania rebeiz, MD       trebeiz@northwell.edu   
Sponsors and Collaborators
Northwell Health
Publications:

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Responsible Party: Tania Rebeiz, Assistant Professor, MD, Northwell Health
ClinicalTrials.gov Identifier: NCT04126408    
Other Study ID Numbers: 1983
First Posted: October 15, 2019    Key Record Dates
Last Update Posted: February 17, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Subarachnoid Hemorrhage
Hemorrhage
Headache
Pathologic Processes
Pain
Neurologic Manifestations
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases