Clinical trial NCT03863704: Transcutaneous VNS to Treat Pediatric IBD
Official title: Transcutaneous Vagal Nerve Stimulation to Treat Pediatric Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn Disease
Ulcerative Colitis
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2019-03-05
Enrollment: 30
Sex: ALL
Minimum age (years): 10
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age 10-21 years
2. IBD diagnosis for at least 3 months, confirmed by clinical, biochemical, and endoscopic evaluations
3. Elevated Fecal calprotectin ≥ 200 ug/g within the past 4 weeks prior to enrollment
4. Evidence of active inflammatory disease despite treatment with at least one conventional therapy
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
   * Prior to baseline calprotectin, 28 days on rectal medication or 2 weeks 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
8. Able and willing to give written informed consent and comply with the requirements of the study protocol.

Exclusion Criteria:

1. Expectation to increase corticosteroids and/or immunosuppressive treatment
2. Presence of bowel stricture with prestenotic dilatation
3. Presence of intra-abdominal or perirectal abscess
4. Pediatric UC activity Index (PUCAI) score ≥ 65 (severe)
5. weighted Pediatric Crohn Disease Activity Index (wPCDAI) score \> 57.5 (severe)
6. Active treatment with antibiotics
7. Presence of active intestinal infection or documented infection by stool PCR or culture analysis in the previous 6 weeks
8. Continuous treatment with an anti-cholinergic medication, including over the counter medications
9. Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators.
10. Current tobacco or nicotine user (to limit potential confounding effects of exposure to nicotine)
11. 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
12. Any planned surgical procedure requiring general anesthesia within the course of the study
13. Participation in any other Investigational drug and/or treatment currently or planned during the length of the study
14. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention
15. Pregnancy or Lactation
16. Comorbid disease with high likelihood of requiring corticosteroid use
17. Inability to comply with study and follow-up procedures
18. Non-English speaking
19. Known cardiac condition causing or with potential to cause arrhythmia

Primary outcomes:
measure: Fecal Calprotectin
timeFrame: 16 weeks
Secondary outcomes:
measure: Change in Whole blood stimulated cytokine levels over time
timeFrame: 16 weeks
measure: Patient Reported Outcome (PRO)
timeFrame: 16 weeks
measure: Pediatric Ulcerative colitis activity index (PUCAI)
timeFrame: 16 weeks
measure: Weighted Pediatric Crohn Disease activity index (wPCDAI)
timeFrame: 16 weeks
measure: Physician Global Assessment (PGA) Score
timeFrame: 16 weeks
measure: Heart Rate Variability (HRV)
timeFrame: 16 weeks
Other outcomes:
Locations:
city: New Hyde Park
country: United States
facility: Steven & Alexandra Cohen Children's Medical Center of New York
state: New York
Study officials:
affiliation: Steven & Alexandra Cohen Children's Medical Center - Northwell Health
name: Benjamin Sahn, MD
role: PRINCIPAL_INVESTIGATOR
References: