NCT07404852

Brief Summary

This is a randomized open-label, with blinded outcome pilot study to evaluate the effect on inflammatory and brain injury laboratory values and explore clinical outcomes in patients who present with ischemic strokes due to large vessel occlusions and are treated with either current accepted management, or accepted management in addition to transcutaneous auricular vagal nerve stimulation.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
65

participants targeted

Target at P50-P75 for not_applicable

Timeline
22mo left

Started Feb 2026

Typical duration 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 Progress12%
Feb 2026Feb 2028

First Submitted

Initial submission to the registry

February 4, 2026

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 12, 2026

Completed
11 days until next milestone

Study Start

First participant enrolled

February 23, 2026

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 29, 2027

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 29, 2028

Last Updated

April 13, 2026

Status Verified

February 1, 2026

Enrollment Period

1.8 years

First QC Date

February 4, 2026

Last Update Submit

April 8, 2026

Conditions

Large Vessel OcclusionAcute Ischemic Stroke

Keywords

Acute ischemic strokelarge vessel occlusioncytokinesvagus nerve stimulatorbrain injury biomarkers

Outcome Measures

Primary Outcomes (5)

  • Brain Derived Tau

    The primary endpoints of the study will include changes in the levels of brain injury biomarkers measured at onset and every 1.5 days till day 7, or discharge (whichever occurs first), this includes: Brain Derived Tau (BD-tau). The investigators will measure BD-tau in aliquots from the plasma with mononuclear antibodies that recognizes a protein of 48 to 68 kilodalton specific to BD-tau. A functional assay will be measured in picogram/milliliter. Will utilize a high sensitivity assays to minimize floor effects.

    7 days

  • Neurofilament light chain

    The primary endpoints of the study will include changes in the levels of brain injury biomarkers measured at onset and every 1.5 days till day 7, or discharge (whichever occurs first), this includes: Neurofilament light chain (NfL). The investigators will measure NfL in aliquots from the plasma with mononuclear antibodies that recognizes a protein of 68-70 kilodalton specific to NfL. A functional assay will be measured in picogram/milliliter. Will utilize a high sensitivity assays to minimize floor effects.

    7 days

  • Interleukin - 1b - Changes and Differences in the Levels

    The primary endpoints of the study will include changes in the levels of inflammatory markers measured at onset and every 1.5 days till day 7, or discharge (whichever occurs first), this includes: Interleukin (IL) -1b. The investigators will measure IL-1b in aliquots from the plasma with mononuclear antibodies that recognizes a protein of 17-31 kilodalton specific to IL-1b. A functional assay will be measured in picogram/milliliter. Will utilize a high sensitivity assays to minimize floor effects.

    7 days

  • Interleukin - 6 - Changes and Differences in the Levels

    The primary endpoints of the study will include changes in the levels of inflammatory markers measured at onset and every 1.5 days till day 7, or discharge (whichever occurs first), this includes: Interleukin (IL) - 6. The investigators will measure IL-6 in aliquots from the plasma with mononuclear antibodies that recognizes a protein of 26 kilodalton specific to IL-6. A functional assay will be measured in picogram/milliliter. Will utilize a high sensitivity assays to minimize floor effects.

    7 days

  • Tumor Necrosis Factor Alpha - Changes and Differences in the Levels

    The primary endpoints of the study will include changes in the levels of inflammatory markers measured at onset and every 1.5 days till day 7, or discharge (whichever occurs first), this includes: Tumor necrosis factor alpha (TNF-a). The investigators will measure IL-1b in aliquots from the plasma with mononuclear antibodies that recognizes a protein of 17 kilodalton specific to TNF-a. A functional assay will be measured in picogram/milliliter. Will utilize a high sensitivity assays to minimize floor effects.

    7 days

Secondary Outcomes (2)

  • Change in NIH Stroke Scale (NIHSS)

    7 days

  • Modified Ranking Scale (mRS)

    90 days

Study Arms (2)

Treatment - Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator

EXPERIMENTAL

All patients will be fitted with the device, the investigator will attach an electrode to the left ear. Stimulation sessions will occur for 20 minutes twice daily during the inpatient period, the investigator will stimulate the auricular branch of the vagus nerve. Patients' will be treated with the following parameters: frequency 20 Hz, pulse width 250 μm, and and a fixed intensity of 0.5 milliampere.

Device: transcutaneous auricular vagal nerve stimulation

Control - No Stimulation Transcutaneous Auricular Vagal Nerve Stimulator

SHAM COMPARATOR

All patients will be fitted with the device, the investigator will attach an electrode to the left ear. Sham stimulation sessions will occur for 20 minutes twice daily during the inpatient period. Patients assigned to the controls arm will have no electricity applied to the auricular branch of the vagus nerve.

Device: Sham transcutaneous vagal nerve stimulation

Interventions

Sham transcutaneous vagal nerve stimulationDEVICE

Patients assigned to the controls arm will have no electricity applied to the Auricular Branch of the Vagus Nerve.

Control - No Stimulation Transcutaneous Auricular Vagal Nerve Stimulator
transcutaneous auricular vagal nerve stimulationDEVICE

Stimulus of the auricular branch of the vagal nerve with the transcutaneous auricular vagal nerve stimulation.

Treatment - Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator

Eligibility Criteria

Age18 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult patients who present with acute ischemic strokes due to large vessel occlusions

You may not qualify if:

  • \<18 years old
  • patients with presumed chronic large vessel occlusions
  • NIHSS\<6
  • pre-morbid modified Rankin score (mRS) \>2
  • unable to initiate treatment under 24 hours from symptom discovery
  • Chronic or acute infection, Recent surgery, active immune disease
  • life expectancy \<3 months
  • patients' undergoing active cancer or immunosuppressive/modulating therapy
  • patients with sustained bradycardia on arrival with a heart rate \<50 beats per minute.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (1)

  • Laurido-Soto OJ, Tan G, Nielsen SS, Huguenard AL, Donovan KM, Xu I, Giles J, Dhar R, Adeoye O, Lee JM, Leuthardt E. Transcutaneous Auricular Vagus Nerve Stimulation Reduces Inflammatory Biomarkers after Large Vessel Occlusion Stroke: Results of a Prospective Randomized Open-Label Blinded Endpoint Trial. Transl Stroke Res. 2025 Dec 22;17(1):7. doi: 10.1007/s12975-025-01405-6.

    PMID: 41428140BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Central Study Contacts

Angela Birke, MS

CONTACT

(314) 362-5291birkea@wustl.edu

Osvaldo Laurido-Soto, MD

CONTACT

314-273-3294ojlaurido-soto@wustl.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Masking Details
Patients enrolled in the trial will be randomized to treatment with electrical stimulation to the auricular branch of the vagus nerve (intervention) or no stimulation to the auricular branch of the vagus nerve (Sham) via an auricular, transcutaneous vagus nerve stimulator. All patients will be fitted with the device, the investigators will attach the electrodes to the left ear. Patients are blinded to the intervention and study personnel will be unblinded, except those performing the laboratory testing and result analyses. Care provider team will be blinded to which treatment group the patient is on.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: This is a randomized open-label, with blinded outcome pilot study to evaluate the effect on inflammatory and brain injury laboratory values and explore clinical outcomes in patients who present with ischemic strokes due to large vessel occlusions and are treated with either current accepted management, or accepted management in addition to transcutaneous auricular vagus nerve stimulation.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Neurology

Study Record Dates

First Submitted

February 4, 2026

First Posted

February 12, 2026

Study Start

February 23, 2026

Primary Completion (Estimated)

November 29, 2027

Study Completion (Estimated)

February 29, 2028

Last Updated

April 13, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

De-identified patient level data may be shared upon reasonable requested and approval by the institutions Human Research Protection Office

Time Frame
Once the trial is finished and publish. Estimated March 2028
Access Criteria
De-identified patient level data may be shared upon reasonable requested and approval by the institutions Human Research Protection Office

Locations

US(1)