NCT05390580: NUVISTA

Neuromodulation Using Vagus Nerve Stimulation Following Ischemic Stroke as Therapeutic Adjunct

Completed NA Results posted Last updated 31 October 2025

What this trial tests

NA trial testing transcutaneous auricular vagal nerve stimulation in Acute Ischemic Stroke in 40 participants. Completed in 23 August 2024.

Timeline

26 September 2022

Primary endpoint
23 August 2024

23 August 2024

Quick facts

Lead sponsor	Washington University School of Medicine
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	single
Primary purpose	treatment
Enrollment	40
Start date	26 September 2022
Primary completion	23 August 2024
Estimated completion	23 August 2024
Sites	1 location across United States

Drugs / interventions tested

• transcutaneous auricular vagal nerve stimulation
• Sham transcutaneous vagal nerve stimulation

Conditions studied

• Acute Ischemic Stroke — all drugs for Acute Ischemic Stroke →

Sponsor

Washington University School of Medicine

Who can join

Adults 18 to 99, any sex, with Acute Ischemic Stroke. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Interleukin - 1b - Changes and Differences in the Levels Primary · 5 days

The primary endpoint was change in inflammatory biomarkers from baseline to day 5, with samples obtained every 1.5 days. Interleukin-1β was the main analyte. Repeated measures were analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker trajectories. Time was modeled quadratically for cytokine and WBC outc

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	-0.222	-0.903 – 0.460
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	0.327	-0.047 – 0.702

Interleukin - 6 - Changes and Differences in the Levels Primary · 5 days

The primary endpoint was change in inflammatory biomarkers from baseline to day 5, with samples obtained every 1.5 days. Interleukin-6 was the main analyte. Repeated measures were analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker trajectories. Time was modeled quadratically for cytokine and WBC outco

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	-4.099	-7.655 – -0.543
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	4.323	2.369 – 6.277

Tumor Necrosis Factor Alpha - Changes and Differences in the Levels Primary · 5 days

The primary endpoint was change in inflammatory biomarkers from baseline to day 5, with samples obtained every 1.5 days. Tumor necrosis factor was the main analyte. Repeated measures were analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker trajectories. Time was modeled quadratically for cytokine and W

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	-0.244	-0.545 – 0.058
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	-0.120	-0.597 – 0.357

White Blood Cell Total Count - Changes and Differences in the Levels Primary · 5 days

The primary endpoint was change in inflammatory biomarkers from baseline to day 5, with samples obtained every 1.5 days. WBC count was the main analyte. Repeated measures were analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker trajectories. Time was modeled quadratically for cytokine and WBC outcomes

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	-0.914	-1.687 – -0.141
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	-0.050	-0.455 – 0.356

Neutrophil to Lymphocyte Ratio - Changes and Differences in the Levels Primary · 5 days

The primary endpoint was change in inflammatory biomarkers from baseline to day 5, with samples obtained every 1.5 days. neutrophil to lymphocyte ratio based on blood samples was the main result of interestse. Repeated measures were planned to be analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker traj

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	NA
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	NA

Change in NIH Stroke Scale (NIHSS) Secondary · 30 days

The secondary endpoint was change in NIHSS from baseline to discharge (\~ day 5) and 30 days. Change in the NIHSS stroke scale number (0-42 and a measure of severity) was the outcome of interest. Repeated measures were analyzed longitudinally using mixed-effects models (FDA guidance), specifying subject as a random effect to account for multiple observations. This approach accommodated irregular timing, missing data, and time-varying covariates. Models included treatment, time since last known normal, and their interaction to test group differences in biomarker trajectories. Time was modeled q

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	-1.613	-2.576 – -0.651
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	-1.562	-5.25 – -0.978

Modified Ranking Scale (mRS) Secondary · 90 days

This is a clinical secondary exploratory endpoints. The Modified Ranking Scale (mRS) is a clinical tool used to assess functional status after suffering a stroke. It ranges from 0 up to 6. It was assessed at day 90. The investigators will assess differences in mRS dependent of the intervention arm. 0 = no symptoms at all 1. = No significant disability despite symptoms; able to carry out all usual duties and activities 2. = Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3. = Moderate disability; requiring some help, but a

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	3.27	± 2.15
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	2.78	± 2.07

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 - Hypotension (C143352) Secondary · 5 days

The investigator will monitor the patient's blood pressure (millimeters of mercury - mmHg) before, during, and after the transauricular vagal nerve stimulation or sham. If hypotension occurs (systolic blood pressure less than 80 mmHg or mean arterial pressure \<60 mmHg) , the investigator will document it and assigned the appropriate grade from 1-5 based on the CTCAE.

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	0
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	2

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 - Sinus Bradycardia (C54940) Secondary · 5 days

The investigator will monitor the patient's heart rate (beat per minute) before, during, and after the transauricular vagal nerve stimulation or sham. If Sinus Bradycardia (C54940) occurs (heart rate less than 60 beats per minute), the investigator will document it and assigned the appropriate grade from 1-5 based on the CTCAE.

Group	Value	95% CI
Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator	2
Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham	4

Adverse events — posted to ClinicalTrials.gov

Time frame: enrollment until end of follow-up (up to 105 days).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Stimulation with Transcutaneous Auricular Vagal Nerve Stimulator

Serious: 0/17 (0%)

Deaths: 3/17

Control - Transcutaneous Auricular Vagal Nerve Stimulator - Sham

Serious: 0/18 (0%)

Deaths: 2/18

Other adverse events (1 terms — click to expand)

Reaction	System	Stimulation with Transcuta…	Control - Transcutaneous A…
The above patient events were bradycardia and hypotension, none were serious.	Cardiac disorders	—	—

Data from ClinicalTrials.gov NCT05390580 adverse events section.

Sponsor's own description

This is a randomized open-label, with blinded outcome pilot study to evaluate the effect on inflammatory 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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.