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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Device: RAVANS; Device: RAVANS-sham

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Benjamin Sahn, MD; Phone Number: 516-472-3650; Email: Bsahn@northwell.edu
• Study Contact Backup: Name: Jillian Charyn; Phone Number: 516-472-3691; Email: jcharyn@northwell.edu

Study Locations

• United States
  • New York
    • Lake Success, New York, United States, 11042
      • Recruiting
      • Feinstein Institute for Medical Research at Northwell Health
      • Principal Investigator: Benjamin Sahn, MD
      • Contact: Jillian Charyn; Phone Number: 516-472-3650; Email: jcharyn@northwell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 39 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cala Health, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2023
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Actual): December 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: IBD-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes