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

NCT ID: NCT07131696

Last Updated: 2025-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-09-30

Study Completion Date

2028-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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tVNS

Group Type EXPERIMENTAL

Transcutaneous Vagal Nerve Stimulation

Intervention Type 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.

Interventions

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Transcutaneous Vagal Nerve Stimulation

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.

Intervention Type DEVICE

Other Intervention Names

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tVNS

Eligibility Criteria

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Inclusion Criteria

* 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
* 18-65 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Marshall Holland

OTHER

Sponsor Role lead

Responsible Party

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Marshall Holland

Assistant Professor of Neurosurgery

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Marshall Holland, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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UAB Hospital

Birmingham, Alabama, United States

Site Status

Countries

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United States

Central Contacts

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Marshall Holland, MD

Role: CONTACT

2059343411

References

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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.

Reference Type BACKGROUND
PMID: 8742988 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8751313 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 40013407 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9787391 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4954928 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2126362 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3332035 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35920945 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10927901 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29603444 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36597947 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22096287 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 60719 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24283706 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24994087 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 7546361 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21116906 (View on PubMed)

Other Identifiers

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IRB-300015166

Identifier Type: -

Identifier Source: org_study_id

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