Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Study in Ulcerative Colitis

Prospective, single-center, sham-controlled, double-blinded 12-week study designed to evaluate the safety and efficacy of the RAVANS device in subjects with Ulcerative Colitis. The goal of the study is to distinguish sham (no stimulation) versus treatment (stimulation) response and to identify treatment responders. The study will last 12 weeks with in-clinic visits at 0 weeks and 12 weeks, and a telehealth-visit at week 6. Additionally, unscheduled visits may occur based on the needs of the subject or at the discretion of the investigator. Subjects will be randomized 2:1 to treatment or sham, and will stimulate at home twice per day.

Inclusion Criteria:Age 10-39 yearsUC diagnosis for at least 3 months, confirmed by standard diagnostic evaluations including clinical, biochemical, and endoscopic studiesIf age 17 years or younger, a PUCAI score of 10-60A partial Mayo score of 3-6If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 14 days before entry into studyIf on 5-Aminosalicylate, dose must be stable with following parameters:28 days on oral medication28 days on or off rectal medicationIf on background immunosuppressive treatment the dose must be stable with the following parameters:56 days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine)112 days (16 weeks) for Infliximab, Adalimumab, Vedolizumab, Ustekinumab, other biologic, tofacitinib, upadacitinib, ozanimodAble and willing to give written informed consent and comply with the requirements of the study protocol.The earbud electrode must fit properly in the prospective subject's left earFecal calprotectin of ≥150 during screening periodExclusion Criteria:Expectation to increase corticosteroids and/or immunosuppressive treatmentPresence of bowel strictureHistory of intra-abdominal or perirectal abscessDisease limited to only rectum (ulcerative proctitis)Active treatment with antibioticsPresence of active intestinal infection or documented infection by stool PCR or culture analysis in the previous 6 weeksContinuous treatment with an anticholinergic medication, including over the counter medications (See appendix)Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.Current tobacco or nicotine user including nicotine patches, gum and vaping (to limit potential confounding effects of exposure to nicotine)Bowel resection surgery within past 90 days prior to study enrollment, or planned surgery within the course of the studyAny planned surgical procedure requiring general anesthesia within the course of the studyParticipation in any other Investigational drug and/or treatment currently or planned during the length of the studyAny condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study interventionPregnancy or LactationComorbid disease with high likelihood of requiring corticosteroid useInability to comply with study and follow-up proceduresIndividuals with prior medical history of significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and AV blocksIndividuals with existing skin lesions on the left ear