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

NCT04126408 | Completed Results FDA Device

• 1 other identifier: 19-0837
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Subarachnoid Hemorrhage, Aneurysmal

Outcome Measures

Primary Outcomes (2)

• 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

  up to 14 days of admission

• Overall Difference in MED at 7 Days

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

  baseline and 7 days

Secondary Outcomes (3)

• The Difference Between the Active and Sham Treatment Groups in the Mean Daily Headache Intensity Pre and Post Stimulation

  up to 14 days of admission

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

  up to 14 days of admission

• Change in SBP Between Active and Sham Group

  before and after stimulation, up to 14 days

Study Arms (2)

Sham arm

SHAM COMPARATOR

gammaCore sham device which will not provide stimulation of the vagus nerve

Device: gammaCore

Treatment group

ACTIVE COMPARATOR

Active gammaCore device that supplies non-invasive stimulation of the cervical branch of the Vagus nerve

Device: gammaCore

Interventions

gammaCore DEVICE

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.

Sham arm; Treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Northshore University Hospital

Manhasset, New York, 11030, United States

Location

Related Publications (15)

• 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.

  PMID: 23808965 BACKGROUND

• 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.

  PMID: 29107164 BACKGROUND

• 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.

  PMID: 26932915 BACKGROUND

• 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.

  PMID: 27704534 BACKGROUND

• 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.

  PMID: 19828484 BACKGROUND

• 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.

  PMID: 24530613 BACKGROUND

• 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.

  PMID: 28286178 BACKGROUND

• 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.

  PMID: 28104084 BACKGROUND

• 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.

  PMID: 20437558 BACKGROUND

• 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.

  PMID: 26645547 BACKGROUND

• 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.

  PMID: 14571320 BACKGROUND

• 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.

  PMID: 30943885 BACKGROUND

• 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.

  PMID: 20633378 BACKGROUND

• 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.

  PMID: 29593576 BACKGROUND

• 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.

  PMID: 30214271 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: northwell health
• Organization: northwell health

trebeiz@northwell.edu

5165620100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, MD

Study Record Dates

• First Submitted: September 13, 2019
• First Posted: October 15, 2019
• Study Start: January 13, 2020
• Primary Completion: June 20, 2022
• Study Completion: June 20, 2022
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)