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

Study Overview
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Brief Summary
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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.

Official Title
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Investigating the Safety and Efficacy of Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) in Ulcerative Colitis (UC) in Pediatric and Young Adult Populations

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Device: RAVANS
* Device: RAVANS-sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 partial Mayo 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 Exclusion Criteria: Expectation to increase corticosteroids and/or immunosuppressive treatment Presence of bowel stricture History of intra-abdominal or perirectal abscess Disease limited to only rectum (ulcerative proctitis) Active treatment with antibiotics 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. 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 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 Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention Pregnancy or Lactation Comorbid disease with high likelihood of requiring corticosteroid use Inability to comply with study and follow-up procedures Individuals with prior medical history of significant arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, sick sinus syndrome, and AV blocks Individuals with existing skin lesions on the left ear

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sham-Controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Two therapy sessions (active stimulation) per day for 12 weeks with Treatment device | Device: RAVANS<br>* Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation<br>|
| Sham Comparator: Sham<br>Two therapy sessions per day for 12 weeks with Sham device (no active stimulation) | Device: RAVANS-sham<br>* RAVANS sham device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Remission | Remission rate in treatment vs sham, assessed by a 0 or 1 point score in the Partial Mayo at week 12 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Responder | Responder rate in treatment vs sham, assessed by greater than or equal to a 2 point reduction in the Partial Mayo score at week 12 | 12 weeks |