The Effect of Transcutaneous Vagal Nerve Stimulation (tVNS) on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage

NCT07131696 | Not Yet Recruiting

• 1 other identifier: IRB-300015166
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The significance of developing a safe and effective therapy for aneurysmal subarachnoid hemorrhage (aSAH) patients suffering cerebral vasospasm (CVS) cannot be overstated. Vasospasm - a clamping down of normal arteries in the days following rupture - remains incredibly challenging to treat.1,2 Current drugs and minimally invasive surgical therapies are helpful, yet woefully insufficient. Symptomatic cerebral vasospasm afflicts about 30% of aneurysmal subarachnoid hemorrhage patients and nearly half will go on to suffer a stroke, despite aggressive medical care.1-3 The autonomic nervous system is a balance between sympathetic (fight or flight) and parasympathetic (rest and digest) influence with sympathetic overactivity and inflammation shown to play an important role in the development and severity of cerebral vasospasm.4,5,17-20 Prior studies of autonomic nervous system neuromodulation highlight its promise as a promising potential avenue to improve morbidity and mortality from CVS in aSAH.6-15 Despite progress, continued high levels of CVS morbidity and mortality stress the urgent need for exploration of neuromodulation therapy. In this proposal, the study team will modulate the autonomic nervous system function in aSAH patients using transcutaneous vagal nerve stimulation (tVNS). tVNS involves placement of a stimulation electrode on the external ear to non-invasively stimulate a branch of the vagal nerve and increase parasympathetic influence. This device has FDA approval for epilepsy and cluster headache. The study hypothesis is that neuromodulation of the autonomic nervous system with tVNS (increasing parasympathetic influence) reduces sympathetic overactivity and inflammation in aSAH resulting in decreased morbidity of CVS.

Conditions

Aneurysmal Subarachnoid Hemorrhage; Vasospasm, Cerebral; Transcutaneous Vagal Nerve Stimulation (tVNS); Endovascular Treatment

Keywords

CVS; aSAH; tVNS

Outcome Measures

Primary Outcomes (3)

• Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid

  Pre-op, Day 1, 2, 7, 10, and discharge (assessed up to 21 days)

• Rate of blood flowing through the brain as assessed by transcranial doppler imaging

  Pre-op, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and discharge (assessed up to 21 days)

• Number of participants experiencing sudden health issues during the study as determined by the need for ventriculoperitoneal shunt placement prior to discharge, length of hospital stay, and disposition upon discharge.

  Pre-op, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and discharge (assessed up to 21 days)

Study Arms (1)

tVNS

EXPERIMENTAL

Device: Transcutaneous Vagal Nerve Stimulation

Interventions

Transcutaneous Vagal Nerve Stimulation DEVICE

Participants will receive up to 4 sessions per day of up to 20-minute stimulation, over the next 10 days of their inpatient hospital stay, following endovascular treatment. Stimulation will be provided by the tVNS device through a small electrode placed around the ear that will send low intensity, pulsed, electrical pulses the vagus nerve.

Also known as: tVNS

tVNS

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or Female
• years of age
• Diagnosed with Fisher grade 3 or 4 aneurysmal subarachnoid hemorrhage
• Ability to undergo endovascular treatment of aneurysmal subarachnoid hemorrhage
• For females of reproductive potential: negative pregnancy test at time of treatment.
• Plan to undergo standard of care treatment and follow-up

You may not qualify if:

• Medically unfit to undergo endovascular treatment (e.g., Hunt Hess grade 5)
• Does not provide consent
• Posterior circulation aneurysmal subarachnoid hemorrhage
• Initial aneurysm treatment after post bleed day 1

Sponsors & Collaborators

• Marshall Holland: lead

Study Sites (1)

UAB Hospital

Birmingham, Alabama, 35233, United States

Location

Related Publications (17)

• Mazzone P, Rodriguez G, Arrigo A, Nobili F, Pisani R, Rosadini G. Cerebral haemodynamic changes induced by spinal cord stimulation in man. Ital J Neurol Sci. 1996 Feb;17(1):55-7. doi: 10.1007/BF01995709.

  PMID: 8742988 BACKGROUND

• Isono M, Kaga A, Fujiki M, Mori T, Hori S. Effect of spinal cord stimulation on cerebral blood flow in cats. Stereotact Funct Neurosurg. 1995;64(1):40-6. doi: 10.1159/000098732.

  PMID: 8751313 BACKGROUND

• Phillips I, Johns MA, Pandza NB, Calloway RC, Karuzis VP, Kuchinsky SE. Three Hundred Hertz Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Impacts Pupil Size Non-Linearly as a Function of Intensity. Psychophysiology. 2025 Feb;62(2):e70011. doi: 10.1111/psyp.70011.

  PMID: 40013407 BACKGROUND

• Tekdemir I, Aslan A, Elhan A. A clinico-anatomic study of the auricular branch of the vagus nerve and Arnold's ear-cough reflex. Surg Radiol Anat. 1998;20(4):253-7.

  PMID: 9787391 BACKGROUND

• White JC. Nervous control of the cerebral vascular system. Clin Neurosurg. 1963;9:67-87. doi: 10.1093/neurosurgery/9.cn_suppl_1.67. No abstract available.

  PMID: 4954928 BACKGROUND

• Edvinsson L, Uddman R, Juul R. Peptidergic innervation of the cerebral circulation. Role in subarachnoid hemorrhage in man. Neurosurg Rev. 1990;13(4):265-72. doi: 10.1007/BF00346363.

  PMID: 2126362 BACKGROUND

• Hara H, Edvinsson L. Perivascular innervation of the cerebral circulation: involvement in the pathophysiology of subarachnoid hemorrhage. Neurosurg Rev. 1987;10(3):171-9. doi: 10.1007/BF01782043.

  PMID: 3332035 BACKGROUND

• Slavin KV, Vannemreddy P. Cervical spinal cord stimulation for prevention and treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: clinical and radiographic outcomes of a prospective single-center clinical pilot study. Acta Neurochir (Wien). 2022 Nov;164(11):2927-2937. doi: 10.1007/s00701-022-05325-4. Epub 2022 Aug 3.

  PMID: 35920945 BACKGROUND

• Takanashi Y, Shinonaga M. Spinal cord stimulation for cerebral vasospasm as prophylaxis. Neurol Med Chir (Tokyo). 2000 Jul;40(7):352-6; discussion 356-7. doi: 10.2176/nmc.40.352.

  PMID: 10927901 BACKGROUND

• Holwerda SW, Holland MT, Reddy CG, Pierce GL. Femoral vascular conductance and peroneal muscle sympathetic nerve activity responses to acute epidural spinal cord stimulation in humans. Exp Physiol. 2018 Jun;103(6):905-915. doi: 10.1113/EP086945. Epub 2018 May 5.

  PMID: 29603444 BACKGROUND

• Bombardieri AM, Albers GW, Rodriguez S, Pileggi M, Steinberg GK, Heit JJ. Percutaneous cervical sympathetic block to treat cerebral vasospasm and delayed cerebral ischemia: a review of the evidence. J Neurointerv Surg. 2023 Dec;15(12):1212-1217. doi: 10.1136/jnis-2022-019838. Epub 2022 Dec 6.

  PMID: 36597947 BACKGROUND

• Jain V, Rath GP, Dash HH, Bithal PK, Chouhan RS, Suri A. Stellate ganglion block for treatment of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage - A preliminary study. J Anaesthesiol Clin Pharmacol. 2011 Oct;27(4):516-21. doi: 10.4103/0970-9185.86598.

  PMID: 22096287 BACKGROUND

• Suzuki J, Iwabuchi T, Hori S. Cervical sympathectomy for cerebral vasospasm after aneurysm rupture. Neurol Med Chir (Tokyo). 1975;15 pt 1:41-50. doi: 10.2176/nmc.15pt1.41. No abstract available.

  PMID: 60719 BACKGROUND

• Wan H, AlHarbi BM, Macdonald RL. Mechanisms, treatment and prevention of cellular injury and death from delayed events after aneurysmal subarachnoid hemorrhage. Expert Opin Pharmacother. 2014 Feb;15(2):231-43. doi: 10.1517/14656566.2014.865724. Epub 2013 Nov 27.

  PMID: 24283706 BACKGROUND

• Baggott CD, Aagaard-Kienitz B. Cerebral vasospasm. Neurosurg Clin N Am. 2014 Jul;25(3):497-528. doi: 10.1016/j.nec.2014.04.008.

  PMID: 24994087 BACKGROUND

• Dorsch NW. Cerebral arterial spasm--a clinical review. Br J Neurosurg. 1995;9(3):403-12. doi: 10.1080/02688699550041403.

  PMID: 7546361 BACKGROUND

• Dorsch N. A clinical review of cerebral vasospasm and delayed ischaemia following aneurysm rupture. Acta Neurochir Suppl. 2011;110(Pt 1):5-6. doi: 10.1007/978-3-7091-0353-1_1.

  PMID: 21116906 BACKGROUND

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Vasospasm, Intracranial

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

Study Officials

• Marshall Holland, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marshall Holland, MD

CONTACT

2059343411; mtholland@uabmc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurosurgery

Study Record Dates

• First Submitted: July 29, 2025
• First Posted: August 20, 2025
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 20, 2025

Record last verified: 2025-08

Locations

US (1)