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

1. Age 10-39 years
2. UC diagnosis for at least 3 months, confirmed by standard diagnostic evaluations including clinical, biochemical, and endoscopic studies
3. If age 17 years or younger, a PUCAI score of 10-60
4. A partial Mayo score of 3-6
5. If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 14 days before entry into study

6. If on 5-Aminosalicylate, dose must be stable with following parameters:

   • 28 days on oral medication
   • 28 days on or off rectal medication

7. If 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, ozanimod
8. Able and willing to give written informed consent and comply with the requirements of the study protocol.
9. The earbud electrode must fit properly in the prospective subject's left ear
10. Fecal calprotectin of ≥150 during screening period

Exclusion Criteria:

1. Expectation to increase corticosteroids and/or immunosuppressive treatment
2. Presence of bowel stricture
3. History of intra-abdominal or perirectal abscess
4. Disease limited to only rectum (ulcerative proctitis)
5. Active treatment with antibiotics
6. Presence of active intestinal infection or documented infection by stool PCR or culture analysis in the previous 6 weeks
7. Continuous treatment with an anticholinergic medication, including over the counter medications (See appendix)
8. Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
9. Current tobacco or nicotine user including nicotine patches, gum and vaping (to limit potential confounding effects of exposure to nicotine)
10. Bowel resection surgery within past 90 days prior to study enrollment, or planned surgery within the course of the study
11. Any planned surgical procedure requiring general anesthesia within the course of the study
12. Participation in any other Investigational drug and/or treatment currently or planned during the length of the study
13. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention
14. Pregnancy or Lactation
15. Comorbid disease with high likelihood of requiring corticosteroid use
16. Inability to comply with study and follow-up procedures
17. Individuals with prior medical history of significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and AV blocks
18. Individuals with existing skin lesions on the left ear