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Subarachnoid Hemorrhage, AneurysmalVANQUISHNCT04126408

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

A study testing gammaCore in people with Subarachnoid Hemorrhage, Aneurysmal, run by Northwell Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Subarachnoid Hemorrhage, Aneurysmal
What is being tested?
gammaCore
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteUnited States
Study dates
13 Jan 2020to 20 Jun 2022
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Northshore University Hospital

    Manhasset, New York, 11030

Other trials in United States

About this study

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.

Read the 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.

Being tested
gammaCore
Medical subject headings
Subarachnoid Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • gammaCoreDevice

    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.

Study groups in NCT04126408
Study groupRoleWhat they receive
Sham armSham comparatorgammaCore sham device which will not provide stimulation of the vagus nerve
Receives: Device: gammaCore
Treatment groupActive comparatorActive gammaCore device that supplies non-invasive stimulation of the cervical branch of the Vagus nerve
Receives: Device: gammaCore

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Difference Between the Active and Sham Treatment Groups in Morphine Equivalence Dosage PER DAY

    Daily morphine equivalence dosage will be calculated and compared between the active and Sham group

    Measured: up to 14 days of admission

  2. Overall Difference in MED at 7 Days

    difference in mean morphine equivalent dosage at 7 days between active and sham group

    Measured: baseline and 7 days

Secondary outcomes (3)
  1. The Difference Between the Active and Sham Treatment Groups in the Mean Daily Headache Intensity Pre and Post Stimulation

    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. least mean square difference between the 2 groups between the pre and post stimulation pain score

    Measured: up to 14 days of admission

  2. The Difference in Device Related Heart Rate Change Before and After Stimulation

    difference in change in Heart rate between the 2 groups from before to after stimulation

    Measured: up to 14 days of admission

  3. Change in SBP Between Active and Sham Group

    difference between pre and post stimulation SBP between the 2 groups

    Measured: before and after stimulation, up to 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2019
  2. Study start13 Jan 2020
  3. Primary completion20 Jun 2022
  4. Study completion20 Jun 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04126408
Sponsor's protocol ID
19-0837
Acronym
VANQUISH
Status last verified
Jan 2024
First submitted
13 Sep 2019
Last updated
9 Jan 2024
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Magalhaes JE, Azevedo-Filho HR, Rocha-Filho PA. The risk of headache attributed to surgical treatment of intracranial aneurysms: a cohort study. Headache. 2013 Nov-Dec;53(10):1613-23. doi: 10.1111/head.12165. Epub 2013 Jun 28.

    PubMed 23808965
  • Rumalla K, Smith KA, Arnold PM, Mittal MK. Subarachnoid Hemorrhage and Readmissions: National Rates, Causes, Risk Factors, and Outcomes in 16,001 Hospitalized Patients. World Neurosurg. 2018 Feb;110:e100-e111. doi: 10.1016/j.wneu.2017.10.089. Epub 2017 Oct 26.

    PubMed 29107164
  • Glisic EK, Gardiner L, Josti L, Dermanelian E, Ridel S, Dziodzio J, McCrum B, Enos B, Lerwick P, Fraser GL, Muscat P, Riker RR, Ecker R, Florman J, Seder DB. Inadequacy of Headache Management After Subarachnoid Hemorrhage. Am J Crit Care. 2016 Mar;25(2):136-43. doi: 10.4037/ajcc2016486.

    PubMed 26932915
  • Morad AH, Tamargo RJ, Gottschalk A. The Longitudinal Course of Pain and Analgesic Therapy Following Aneurysmal Subarachnoid Hemorrhage: A Cohort Study. Headache. 2016 Nov;56(10):1617-1625. doi: 10.1111/head.12908. Epub 2016 Oct 5.

    PubMed 27704534
  • Dorhout Mees SM, Bertens D, van der Worp HB, Rinkel GJ, van den Bergh WM. Magnesium and headache after aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2010 May;81(5):490-3. doi: 10.1136/jnnp.2009.181404. Epub 2009 Oct 13.

    PubMed 19828484
  • Oshinsky ML, Murphy AL, Hekierski H Jr, Cooper M, Simon BJ. Noninvasive vagus nerve stimulation as treatment for trigeminal allodynia. Pain. 2014 May;155(5):1037-1042. doi: 10.1016/j.pain.2014.02.009. Epub 2014 Feb 14.

    PubMed 24530613
  • Akerman S, Simon B, Romero-Reyes M. Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache. Neurobiol Dis. 2017 Jun;102:96-104. doi: 10.1016/j.nbd.2017.03.004. Epub 2017 Mar 9.

    PubMed 28286178
  • Frangos E, Komisaruk BR. Access to Vagal Projections via Cutaneous Electrical Stimulation of the Neck: fMRI Evidence in Healthy Humans. Brain Stimul. 2017 Jan-Feb;10(1):19-27. doi: 10.1016/j.brs.2016.10.008. Epub 2016 Oct 20.

    PubMed 28104084
  • Bosche B, Graf R, Ernestus RI, Dohmen C, Reithmeier T, Brinker G, Strong AJ, Dreier JP, Woitzik J; Members of the Cooperative Study of Brain Injury Depolarizations (COSBID). Recurrent spreading depolarizations after subarachnoid hemorrhage decreases oxygen availability in human cerebral cortex. Ann Neurol. 2010 May;67(5):607-17. doi: 10.1002/ana.21943.

    PubMed 20437558
  • Chen SP, Ay I, Lopes de Morais A, Qin T, Zheng Y, Sadeghian H, Oka F, Simon B, Eikermann-Haerter K, Ayata C. Vagus nerve stimulation inhibits cortical spreading depression. Pain. 2016 Apr;157(4):797-805. doi: 10.1097/j.pain.0000000000000437.

    PubMed 26645547
  • Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003 May-Aug;9(5-8):125-34.

    PubMed 14571320
  • Suzuki T, Takizawa T, Kamio Y, Qin T, Hashimoto T, Fujii Y, Murayama Y, Patel AB, Ayata C. Noninvasive Vagus Nerve Stimulation Prevents Ruptures and Improves Outcomes in a Model of Intracranial Aneurysm in Mice. Stroke. 2019 May;50(5):1216-1223. doi: 10.1161/STROKEAHA.118.023928.

    PubMed 30943885
  • George MS, Ward HE Jr, Ninan PT, Pollack M, Nahas Z, Anderson B, Kose S, Howland RH, Goodman WK, Ballenger JC. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul. 2008 Apr;1(2):112-21. doi: 10.1016/j.brs.2008.02.001. Epub 2008 Mar 28.

    PubMed 20633378
  • Breit S, Kupferberg A, Rogler G, Hasler G. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018 Mar 13;9:44. doi: 10.3389/fpsyt.2018.00044. eCollection 2018.

    PubMed 29593576
  • Lendvai IS, Maier A, Scheele D, Hurlemann R, Kinfe TM. Spotlight on cervical vagus nerve stimulation for the treatment of primary headache disorders: a review. J Pain Res. 2018 Aug 27;11:1613-1625. doi: 10.2147/JPR.S129202. eCollection 2018.

    PubMed 30214271

Questions about this trial

What is this clinical trial studying?

A study testing gammaCore in people with Subarachnoid Hemorrhage, Aneurysmal, run by Northwell Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Difference Between the Active and Sham Treatment Groups in Morphine Equivalence Dosage PER DAY (time frame: up to 14 days of admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04126408, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.

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