This will be a single-arm, open-label trial to assess the brain blood oxygen saturation and EEG of hospitalized patients with delirium, and to assess feasibility and safety of transauricular vagus nerve stimulation (taVNS) in this population. This is an early feasibility study and there is no randomization or placebo group. All patients enrolled will receive taVNS in addition to usual hospital care for delirium. We aim to recruit 10 patients. Patients will be recruited from an inpatient population in the ICU or hospital unit. Candidates will be identified on daily rounds by a primary medical team. A diagnosis of delirium will be confirmed by a physician trained in psychiatry, neurology or neurocritical care. After inclusion and exclusion are reviewed, a baseline assessment of delirium through the CAM-ICU (Confusion Assessment Method for Intensive Care Unit) will be completed. After screening and informed consent, the patient will be considered as entered into the study. The patient will begin taVNS within 24 hours of enrollment. Patients who are consented but do not begin taVNS within 24 hours will require repeat screening to evaluate updates to clinical condition and repeat CAM-ICU score to ensure they continue to meet inclusion criteria.
We anticipate that in most situations, a legally authorized representative for the patient will be the initial contact for the study as well as the individual providing consent to the study. If a patient were to meet exclusion criteria after enrollment, they would be ineligible for further participation. Previously collected data prior to the event would still be used for analysis.
The study device is the Soterix Medical Transcutaneous auricular Vagus Nerve Stimulator, for which we have submitted an IDE to the FDA and received nonsignificant risk designation (NSR). The device will be configured with the Soterix Medical RELIfit-Tragus accessory to hook around the ear to deliver stimulation to the auricular branch of the vagus nerve in the tragus of the left ear. TaVNS will be performed on the left side to minimize the already negligible risk of cardiac side effects. The device will be set to a frequency of 25 Hz and pulse width of 500 μs based on previous literature. The intensity will be titrated in the first session to a barely perceptible threshold. Patients unable to cooperate with the titration procedure will have their stimulation intensity set at 1.25 mA.
Vitals, relevant medical history, labs and medication data will be collected from the medical record. Prior to initiation of taVNS on the first day, subjects will undergo 10 minutes of neurophysiological monitoring to determine baseline recording. Cerebral oxygenation, hemodynamics, and EEG will be documented using the Masimo O3/Sedline brain monitoring system, a noninvasive, commercially available brain monitor. The Masimo O3/Sedline device will continue to be used to monitor the patient while undergoing taVNS to record further data for another 10 minutes during the first stimulation session.
Subjects will be prescribed two 30-minute sessions of taVNS stimulation each day with a minimum of 6 hours between sessions for a maximum of 7 days until either delirium resolves, or the patient is discharged.
Upon discontinuation of the study, we will screen the subject for any sensory changes, discomfort, or adverse events, as well as perform an additional CAM-ICU screen. The subject will be discharged without follow-up due to the minimal risk in the study. Risks and adverse events associated with use of the Soterix Medical Transcutaneous auricular Vagus Nerve Stimulator are small. We ensure patients use the device only under supervision by the research team, with proper application, and perform regular skin inspections after each stimulation session. Subjects will be supervised during monitoring by study personnel who will observe for any evidence of subject discomfort from monitoring. A member of the study team who is a Stony Brook University Hospital ICU attending intensivist will be present throughout each stimulation session, as well as for the initial device intensity titration. A review of pre- and post-session relevant clinical data (including vitals, medications, skin inspection and labs) will be performed.
All enrolled patients who receive at least one session of taVNS will be included in the final analysis. Patients with incomplete data will be reported and analyzed using available data only, without imputation. Due to the nature of ICU care, compliance with the protocol will be defined as completing at least 1 stimulation session during the 7-day study period.
