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

Обзор

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.

Вмешательства

• Устройство 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.

Первичные конечные точки

• Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: Pre-op, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and discharge (assessed up to 21 days)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UAB Hospital — Birmingham

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07131696 · IRB-300015166

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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