NCT04557618

Brief Summary

This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following spontaneous subarachnoid hemorrhage.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
31mo left

Started Jan 2021

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress67%
Jan 2021Dec 2028

First Submitted

Initial submission to the registry

September 4, 2020

Completed
17 days until next milestone

First Posted

Study publicly available on registry

September 21, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

January 5, 2021

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2026

Expected
2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

December 26, 2025

Status Verified

December 1, 2025

Enrollment Period

5.4 years

First QC Date

September 4, 2020

Last Update Submit

December 18, 2025

Conditions

Subarachnoid Hemorrhage

Keywords

Vagal nerve stimulation

Outcome Measures

Primary Outcomes (6)

  • Inflammatory markers in the serum on admission

    TNF alpha from blood draw

    On hospital day 1

  • Change in inflammatory markers in the serum

    TNF alpha from blood draws

    Through hospital admission, average of 4 weeks

  • Inflammatory markers in the CSF on admission

    TNF alpha from cerebrospinal fluid

    On hospital day 1

  • Change in inflammatory markers in the CSF

    TNF alpha from cerebrospinal fluid

    Through hospital admission, average of 4 weeks

  • Cerebral vasospasm

    Presence of moderate/severe radiographic vasospasm

    Through hospital admission, average of 4 weeks

  • Hydrocephalus

    Need for permanent CSF diversion via a ventricular shunt

    Through hospital admission, average of 4 weeks

Secondary Outcomes (9)

  • Inflammatory markers in the serum on admission

    On hospital day 1

  • Change in inflammatory markers in the serum

    Through hospital admission, average of 4 weeks

  • Inflammatory markers in the CSF on admission

    On hospital day 1

  • Change in inflammatory markers in the CSF

    Through hospital admission, average of 4 weeks

  • Cerebral vasospasm

    Through hospital admission, average of 4 weeks

  • +4 more secondary outcomes

Study Arms (2)

Auricular VNS Stimulation

EXPERIMENTAL

Participants receive twice daily auricular vagal nerve stimulation

Device: Auricular Vagus Nerve Stimulation

Sham Auricular VNS Stimulation

SHAM COMPARATOR

Participants will have an auricular vagal nerve stimulator applied twice daily, without the stimulation applied

Device: Sham Auricular Vagus nerve Stimulation

Interventions

Sham Auricular Vagus nerve StimulationDEVICE

Transcutaneous auricular vagal nerve ear clip applied without current

Sham Auricular VNS Stimulation
Auricular Vagus Nerve StimulationDEVICE

Transcutaneous auricular vagal nerve stimulation

Auricular VNS Stimulation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Spontaneous subarachnoid hemorrhage

You may not qualify if:

  • Trauma-induced subarachnoid hemorrhage
  • Ongoing chemotherapy
  • Taking immunosuppressive medications for other medical illnesses
  • Presence of a pacemaker
  • Prolonged bradycardia at time of admission

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (5)

  • Tan G, Huguenard AL, Donovan KM, Demarest P, Liu X, Li Z, Adamek M, Lavine K, Vellimana AK, Kummer TT, Osbun JW, Zipfel GJ, Brunner P, Leuthardt EC. The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial. Elife. 2025 Jan 9;13:RP100088. doi: 10.7554/eLife.100088.

    PMID: 39786346DERIVED

  • Huguenard A, Tan G, Johnson G, Adamek M, Coxon A, Kummer T, Osbun J, Vellimana A, Limbrick D Jr, Zipfel G, Brunner P, Leuthardt E. Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial. PLoS One. 2024 Aug 23;19(8):e0301154. doi: 10.1371/journal.pone.0301154. eCollection 2024.

    PMID: 39178291DERIVED

  • Huguenard AL, Tan G, Rivet DJ, Gao F, Johnson GW, Adamek M, Coxon AT, Kummer TT, Osbun JW, Vellimana AK, Limbrick DD, Zipfel GJ, Brunner P, Leuthardt EC. Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial. medRxiv [Preprint]. 2024 May 1:2024.04.29.24306598. doi: 10.1101/2024.04.29.24306598.

    PMID: 38746275DERIVED

  • Tan G, Huguenard AL, Donovan KM, Demarest P, Liu X, Li Z, Adamek M, Lavine K, Vellimana AK, Kummer TT, Osbun JW, Zipfel GJ, Brunner P, Leuthardt EC. The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study. medRxiv [Preprint]. 2024 Sep 8:2024.04.03.24304759. doi: 10.1101/2024.04.03.24304759.

    PMID: 38633771DERIVED

  • Huguenard AL, Tan G, Johnson GW, Adamek M, Coxon AT, Kummer TT, Osbun JW, Vellimana AK, Limbrick DD Jr, Zipfel GJ, Brunner P, Leuthardt EC. Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH): Protocol for a prospective, triple-blinded, randomized controlled trial. medRxiv [Preprint]. 2024 Mar 19:2024.03.18.24304239. doi: 10.1101/2024.03.18.24304239.

    PMID: 38562875DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Eric C Leuthardt, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna L Huguenard, MD

CONTACT

3144506698ahuguenard@wustl.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Masking Details
All participants will be fitted with an auricular stimulator, but blinded to whether they are receiving stimulation or not. Outcome scores will be assessed and recorded by clinicians blinded to treatment arm.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants are assigned to either stimulation or sham stimulation arms
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Assistant Professor of Neurosurgery

Study Record Dates

First Submitted

September 4, 2020

First Posted

September 21, 2020

Study Start

January 5, 2021

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2028

Last Updated

December 26, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)