Aneurysmal Subarachnoid HemorrhageNCT07131696
The Effect of Transcutaneous Vagal Nerve Stimulation (tVNS) on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage
A study testing Transcutaneous Vagal Nerve Stimulation in people with Aneurysmal Subarachnoid Hemorrhage and Vasospasm, Cerebral, run by Marshall Holland at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Aneurysmal Subarachnoid Hemorrhage, Vasospasm, Cerebral, Transcutaneous Vagal Nerve Stimulation (tVNS)
- What is being tested?
- Transcutaneous Vagal Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Feb 2026to Sep 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UAB Hospital
Birmingham, Alabama, 35233
Marshall Holland Assistant Professor of Neurosurgery
About this study
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
- Being tested
- Transcutaneous Vagal Nerve Stimulation
- Keywords
- CVS, aSAH, tVNS
- Medical subject headings
- Subarachnoid Hemorrhage, Vasospasm, Intracranial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Vagal Nerve StimulationDevice
Also called tVNS
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.
| Study group | Role | What they receive |
|---|---|---|
| tVNS | Experimental | Not described Receives: Device: Transcutaneous Vagal Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid
Measured: 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
Measured: 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.
Measured: Pre-op, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and discharge (assessed up to 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2025
- Study start6 Feb 2026
- Primary completionSep 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Aneurysmal Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marshall Holland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marshall Holland, University of Alabama at Birmingham
- Investigators
- Marshall Holland, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07131696
- Sponsor's protocol ID
- IRB-300015166
- Other IDs
- UAB
- Status last verified
- Aug 2026
- First submitted
- 29 Jul 2025
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 8742988Isono 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.
PubMed 8751313Phillips 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.
PubMed 40013407Tekdemir 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.
PubMed 9787391White 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.
PubMed 4954928Edvinsson 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.
PubMed 2126362Hara 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.
PubMed 3332035Slavin 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.
PubMed 35920945Takanashi 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.
PubMed 10927901Holwerda 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.
PubMed 29603444Bombardieri 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.
PubMed 36597947Jain 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.
PubMed 22096287Suzuki 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.
PubMed 60719Wan 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.
PubMed 24283706Baggott CD, Aagaard-Kienitz B. Cerebral vasospasm. Neurosurg Clin N Am. 2014 Jul;25(3):497-528. doi: 10.1016/j.nec.2014.04.008.
PubMed 24994087
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Transcutaneous Vagal Nerve Stimulation (tVNS) on Cerebral Vasospasm Secondary to Aneurysmal Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT07131696
- Acronym / sponsor ID
- IRB-300015166
- Conditions
- Aneurysmal Subarachnoid Hemorrhage, Vasospasm, Cerebral, Transcutaneous Vagal Nerve Stimulation (tVNS), Endovascular Treatment
- Keywords
- CVS, aSAH, tVNS
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Marshall HollandUniversity, hospital or other
- Study start
- 6 Feb 2026 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 20 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tVNS | Experimental | Device: Transcutaneous Vagal Nerve Stimulation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous Vagal Nerve StimulationAlso: tVNSParticipants 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. | Device | tVNS |
Primary outcome
Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid
Time frame: 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
Time frame: 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.
Time frame: Pre-op, Day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and discharge (assessed up to 21 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Background: PubMed 8742988Mazzone 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.
- Background: PubMed 8751313Isono 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.
- Background: PubMed 40013407Phillips 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.
- Background: PubMed 9787391Tekdemir 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.
- Background: PubMed 4954928White 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.
- Background: PubMed 2126362Edvinsson 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.
- Background: PubMed 3332035Hara 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.
- Background: PubMed 35920945Slavin 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.
- Background: PubMed 10927901Takanashi 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.
- Background: PubMed 29603444Holwerda 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.
- Background: PubMed 36597947Bombardieri 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.
- Background: PubMed 22096287Jain 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marshall Holland, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Vagal Nerve Stimulation in people with Aneurysmal Subarachnoid Hemorrhage and Vasospasm, Cerebral, run by Marshall Holland 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 8 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 11 Aug 2026. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marshall Holland, MD (2059343411, mtholland@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants affected by cerebral inflammation during the course of the study as assessed by laboratory markers in blood and cerebral spinal fluid (time frame: Pre-op, Day 1, 2, 7, 10, and discharge (assessed up to 21 days)). The study lists 3 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 NCT07131696, which also lists 17 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 11 Aug 2026.