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

Prior treatment

• Expectation to increase corticosteroids and/or immunosuppressive treatment
• Presence of active intestinal infection or documented infection by stool PCR or culture analysis in the previous 6 weeks
• Continuous 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.
• Bowel resection surgery within past 90 days prior to study enrollment, or planned surgery within the course of the study
• Any planned surgical procedure requiring general anesthesia within the course of the study
• Participation in any other Investigational drug and/or treatment currently or planned during the length of the study
• Individuals with prior medical history of significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and AV blocks

Other illness

• History of intra-abdominal or perirectal abscess
• Disease limited to only rectum (ulcerative proctitis)
• Antibiotic treatment for active infection
• Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention
• Comorbid disease with high likelihood of requiring corticosteroid use

Other

• Presence of bowel stricture
• Current tobacco or nicotine user including nicotine patches, gum and vaping (to limit potential confounding effects of exposure to nicotine)
• Pregnancy or Lactation
• Inability to comply with study and follow-up procedures
• Individuals with existing skin lesions on the left ear

• Age 10-39 years
• UC diagnosis for at least 3 months, confirmed by standard diagnostic evaluations including clinical, biochemical, and endoscopic studies
• If age 17 years or younger, a PUCAI score of 10-60
• A modification of UCDAI score of 3-6
• If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 14 days before entry into study
• If on 5-Aminosalicylate, dose must be stable with following parameters:
  • 28 days on oral medication
  • 28 days on or off rectal medication
• 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
• Able 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 ear
• Fecal calprotectin of ≥150 during screening period