Transcutaneous VNS to Treat Pediatric IBD

NCT03863704 | Completed DMC FDA Device

• 1 other identifier: 18-0945
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The current available therapies for inflammatory bowel disease (IBD), including immunomodulator and biologic medications may have toxicities limiting use or inadequate effect. We propose a novel approach to the treatment of IBD by using transcutaneous vagal nerve stimulation (VNS). Research has previously identified that VNS using a surgically implanted stimulator can improve symptoms and decrease inflammation in people with inflammatory diseases. This study will evaluate the use of non-invasive nerve stimulation through the skin (rather than through an implanted device) as a potential therapy in pediatric patients with Crohn Disease or ulcerative colitis. We will be evaluating how this nerve stimulation affects symptoms, markers of inflammation found in the blood and stool including cytokine levels, and heart rate variability. The primary hypothesis of the study is the use of transcutaneous VNS will decrease inflammation in people with IBD leading to improved signs and symptoms of disease. The primary endpoint of the study is to evaluate the change in fecal calprotectin after 16 weeks of nerve stimulation. Secondary endpoints include changes in symptom scores, blood cytokine levels, and heart rate variability.

Conditions

Crohn Disease; Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Fecal Calprotectin

  Change in fecal calprotectin over time

  16 weeks

Secondary Outcomes (6)

• Change in Whole blood stimulated cytokine levels over time

  16 weeks

• Patient Reported Outcome (PRO)

  16 weeks

• Pediatric Ulcerative colitis activity index (PUCAI)

  16 weeks

• Weighted Pediatric Crohn Disease activity index (wPCDAI)

  16 weeks

• Physician Global Assessment (PGA) Score

  16 weeks

Study Arms (3)

nerve stimulation ear then leg

SHAM COMPARATOR

Subjects in this arm will be randomized to receive nerve stimulation with TENS of the ear followed by leg stimulation

Device: Transcutaneous Electrical Nerve Stimulation (TENS)

nerve stimulation leg then ear

SHAM COMPARATOR

Subjects in this arm will be randomized to receive leg nerve stimulation with TENS followed by ear nerve stimulation

Device: Transcutaneous Electrical Nerve Stimulation (TENS)

Subjects receiving Infliximab

OTHER

Subjects on Infliximab as part of their clinical care will not be randomized as the study treatment for these subjects will be the same. The sham arm is not included for patients on infliximab.

Device: Transcutaneous Electrical Nerve Stimulation (TENS)

Interventions

Transcutaneous Electrical Nerve Stimulation (TENS) DEVICE

To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg.

Subjects receiving Infliximab; nerve stimulation ear then leg; nerve stimulation leg then ear

Eligibility Criteria

• Age: 10 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 10-21 years
• IBD diagnosis for at least 3 months, confirmed by clinical, biochemical, and endoscopic evaluations
• Elevated Fecal calprotectin ≥ 200 ug/g within the past 4 weeks prior to enrollment
• Evidence of active inflammatory disease despite treatment with at least one conventional therapy
• 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:
• days on oral medication
• Prior to baseline calprotectin, 28 days on rectal medication or 2 weeks off rectal medication
• If on background immunosuppressive treatment the dose must be stable with the following parameters:
• days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine)
• days (16 weeks) for Infliximab, Adalimumab, Vedolizumab, Ustekinumab, other biologic
• Able and willing to give written informed consent and comply with the requirements of the study protocol.

You may not qualify if:

• Expectation to increase corticosteroids and/or immunosuppressive treatment
• Presence of bowel stricture with prestenotic dilatation
• Presence of intra-abdominal or perirectal abscess
• Pediatric UC activity Index (PUCAI) score ≥ 65 (severe)
• weighted Pediatric Crohn Disease Activity Index (wPCDAI) score \> 57.5 (severe)
• 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 anti-cholinergic medication, including over the counter medications
• Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
• Current tobacco or nicotine user (to limit potential confounding effects of exposure to nicotine)
• Bowel resection surgery within past 90 days prior to study enrollment and on no conventional IBD therapy, 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

Sponsors & Collaborators

• Northwell Health: lead

Study Sites (1)

Steven & Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11042, United States

Location

Related Publications (1)

• Sahn B, Pascuma K, Kohn N, Tracey KJ, Markowitz JF. Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial. Bioelectron Med. 2023 Oct 18;9(1):23. doi: 10.1186/s42234-023-00124-3.

  PMID: 37849000 DERIVED

MeSH Terms

Conditions

Crohn Disease; Colitis, Ulcerative

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Study Officials

• Benjamin Sahn, MD

  Steven & Alexandra Cohen Children's Medical Center - Northwell Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will be given two possible anatomic sites to apply nerve stimulation, one of which is known to induce vagal nerve stimulation and the other does not.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: March 5, 2019
• Study Start: February 14, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)