TaVNS for Delirium

NCT07258082 | Recruiting FDA Device

• 1 other identifier: IRB2025-00131
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test whether a non-invasive device called transauricular vagus nerve stimulation (taVNS) is safe, practical, and potentially helpful for patients in the hospital who develop delirium. Delirium is a state of confusion that often happens to people in the hospital who are sick or hurt. It can cause agitation, trouble paying attention and difficulty understanding what is happening. Delirium may slow overall recovery. This study will focus on feasibility and safety. Researchers want to learn whether taVNS can be given safely to critically-ill patients, whether patients and staff can tolerate the treatments, and whether the device produces measurable changes in brain activity and brain oxygen levels. The main questions this study aims to answer are:

• Is it possible to deliver taVNS safely and consistently to patients in the ICU who have delirium?
• Do patients tolerate the device without significant side effects or complications?
• Does taVNS cause short-term changes in brain signals and oxygen levels that may suggest effects on brain function? This is an early feasibility study and there is no randomization or placebo group. All patients enrolled will receive taVNS in addition to their usual hospital care for delirium. What participants will do:
• Be identified by their hospital care team and have a confirmed diagnosis of delirium.
• Provide consent (or have a legally authorized representative provide consent if the patient cannot.)
• Undergo brief assessments of thinking and attention (for example, the ICDSC test.)
• Receive taVNS treatment using a small clip electrode placed on the ear.
• The device sends gentle electrical pulses to the nerve in the ear.
• Each session lasts about 30 minutes, given twice per day (morning and evening, with at least 6 hours between sessions).
• Treatment can continue for up to 7 days while the patient is in the ICU.
• Be monitored during and after each session. The study team will check vital signs, examine the ear for irritation, and ask about any discomfort.
• On the first day, researchers will also record brain signals (EEG) and brain oxygen levels before and during stimulation using FDA-approved hospital monitoring devices. Possible risks and discomforts:
• Mild side effects are possible, such as tingling, a tickling or pricking feeling in the ear, or temporary skin redness where the clip is placed.
• Serious side effects are not expected, but all patients will be closely monitored during and after each session to ensure safety. Possible benefits:
• Patients may or may not experience personal benefit. The main benefit is helping researchers learn whether this treatment approach is safe and practical. In the future, taVNS could potentially become a new tool to help treat or prevent delirium in hospitalized patients. Study size and duration:
• The study will enroll a limited number of ICU patients with delirium at Stony Brook University Hospital.
• Patients may take part for up to 7 days while hospitalized. Who can join:
• Right-handed, adult patients in the ICU who are diagnosed with delirium.
• People with certain medical conditions (such as brain bleeds, new strokes, pacemakers or other contraindications) may not be able to participate, for safety reasons.

Conditions

Delirium Treatment; Delirium

Keywords

delirium; tavns; transauricular vagus nerve stimulation; vagus nerve stimulation; transcutaneous vagus nerve stimulation

Outcome Measures

Primary Outcomes (2)

• Feasibility of taVNS in hospitalized patients with delirium

  We will assess feasibility of taVNS as follows: The proportion of stimulation delivered relative to the stimulation prescribed, calculated as: Stimulation delivered (minutes) /Stimulation prescribed (minutes) Feasibility will be demonstrated if: 1. The mean proportion of stimulation delivered across the cohort is ≥10%. Previous taVNS studies in adults have demonstrated that as little as 6 minutes of stimulation is adequate to demonstrate neuromodulatory effect as detected by fMRI. In our protocol, patients will be prescribed a total of 60 minutes of stimulation per day of study 6 minutes of stimulation (a known minimum effective dose) is thus 10% of prescribed stimulation time. 2. At least 80% of patients achieve ≥10% of prescribed stimulation.

  From enrollment to end of treatment at a maximum of 7 days

• Feasibility of taVNS in delirious hospitalized patients

  We will assess feasibility of taVNS as follows: The proportion of stimulation delivered relative to the stimulation prescribed, calculated as: Stimulation delivered (minutes) / Stimulation prescribed (minutes) Feasibility will be demonstrated if: 1. The mean proportion of stimulation delivered across the cohort is ≥10%. Previous taVNS studies in adults have demonstrated that as little as 6 minutes of stimulation is adequate to demonstrate neuromodulatory effect as detected by fMRI. In our protocol, patients will be prescribed a total of 60 minutes of stimulation per day of study. 6 minutes of stimulation (a known minimum effective dose) is thus 10% of prescribed stimulation time. 2. At least 80% of patients achieve ≥10% of prescribed stimulation.

  From enrollment to the end of study at a maximum of 7 days

Study Arms (1)

TaVNS and Usual Care for Delirium

EXPERIMENTAL

Hospitalized, right-hand-dominant adults (age ≥ 22) with delirium, receive transauricular vagus nerve stimulation (taVNS) in addition to standard clinical management. TaVNS is administered twice a day, for a maximum of 7 days, until delirium resolves or the patient is discharged from the ICU.

Device: Transauricular Vagus Nerve Stimulation

Interventions

Transauricular Vagus Nerve Stimulation DEVICE

TaVNS starts within 24 hours of consent and is given twice daily (\~30 minutes per session, ≥6 hours apart) for up to 7 days or until delirium resolves. Stimulation will be delivered to the tragus of the left ear via non-invasive clip-on electrode. Stimulation parameters will be set to: pulse width 500 µs, frequency 25 Hz, 30 s on / 30 s off. Current amplitude will be titrated to perceptual threshold (0.5-5.0 mA); if patients are unable to participate in perceptual threshold titration, then 0.6 mA will be utilized. On the first day of stimulation, patients will undergo 10 minutes of baseline EEG and cerebral oximetry, followed by 10 minutes of EEG and cerebral oximetry during taVNS.

TaVNS and Usual Care for Delirium

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stony Brook University Hospital inpatient, Age \> 22
• Right- handed
• Screen positive for delirium on ICDSC instrument

You may not qualify if:

• Severe neurologic disability including severe traumatic brain injury, severe permanent cognitive impairment
• Pacemaker present
• Implanted VNS stimulator present
• Personal history of epilepsy
• Facial or ear pain or trauma
• Recent history of substance abuse
• Any other medical condition that, in the judgment of the investigator, makes participation in the study unsafe.
• Weight \< 40kg
• Pregnant females
• Intubated patient

Sponsors & Collaborators

• Stony Brook University: lead

Study Sites (1)

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

RECRUITING

Related Publications (4)

• Wilson JE, Mart MF, Cunningham C, Shehabi Y, Girard TD, MacLullich AMJ, Slooter AJC, Ely EW. Delirium. Nat Rev Dis Primers. 2020 Nov 12;6(1):90. doi: 10.1038/s41572-020-00223-4.

  PMID: 33184265 BACKGROUND

• Huffman WJ, Subramaniyan S, Rodriguiz RM, Wetsel WC, Grill WM, Terrando N. Modulation of neuroinflammation and memory dysfunction using percutaneous vagus nerve stimulation in mice. Brain Stimul. 2019 Jan-Feb;12(1):19-29. doi: 10.1016/j.brs.2018.10.005. Epub 2018 Oct 9.

  PMID: 30337243 BACKGROUND

• Badran BW, Dowdle LT, Mithoefer OJ, LaBate NT, Coatsworth J, Brown JC, DeVries WH, Austelle CW, McTeague LM, George MS. Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review. Brain Stimul. 2018 May-Jun;11(3):492-500. doi: 10.1016/j.brs.2017.12.009. Epub 2017 Dec 29.

  PMID: 29361441 BACKGROUND

• Hshieh TT, Fong TG, Marcantonio ER, Inouye SK. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. J Gerontol A Biol Sci Med Sci. 2008 Jul;63(7):764-72. doi: 10.1093/gerona/63.7.764.

  PMID: 18693233 BACKGROUND

MeSH Terms

Conditions

Delirium

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Isadora Botwinick, MD

  Stony Brook University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isadora Botwinick, MD

CONTACT

631-444-8329; isadora.botwinick@stonybrookmedicine.edu

Charles Mikell, MD

CONTACT

631-444-9137; charles.mikell@stonybrookmedicine.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor of Surgery

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start: September 26, 2025
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD and supporting information will be available starting 6 months after publication.

Locations

US (1)