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Transcutaneous VNS to Treat Pediatric IBD (STIMIBD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03863704
Recruitment Status : Recruiting
First Posted : March 5, 2019
Last Update Posted : July 13, 2020
Sponsor:
Information provided by (Responsible Party):
Northwell Health

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.

Condition or disease Intervention/treatment Phase
Crohn Disease Ulcerative Colitis Device: Transcutaneous Electrical Nerve Stimulation (TENS) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Transcutaneous Vagal Nerve Stimulation to Treat Pediatric Inflammatory Bowel Disease
Actual Study Start Date : February 14, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Sham Comparator: nerve stimulation ear then leg
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)
To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg.

Sham Comparator: nerve stimulation leg then ear
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)
To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg.

Subjects receiving Infliximab
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)
To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg.




Primary Outcome Measures :
  1. Fecal Calprotectin [ Time Frame: 16 weeks ]
    Change in fecal calprotectin over time


Secondary Outcome Measures :
  1. Change in Whole blood stimulated cytokine levels over time [ Time Frame: 16 weeks ]
    Blood will be collected into 2 tubes, one with no stimulant and the other with lipopolysaccharide (LPS) to stimulate macrophages to produce cytokines. Cytokine levels within the blood will be assessed and compared to baseline levels. The cytokines being assayed include tumor necrosis factor-alpha, Interferon-gamma, Transforming Growth Factor-beta and Interleukins (IL) - 1, 6, 10, 12, 17, 18, 23. Samples will be collected for this analysis at week 0, 2, 4, and 24

  2. Patient Reported Outcome (PRO) [ Time Frame: 16 weeks ]
    PROMIS Pediatric Profile v2.0-25 and PROMIS Parent Proxy v2.0- 25 questionnaires to evaluate the effect of VNS on abdominal pain intensity and interference in daily activities, fatigue, anxiety, depression, physical function and peer relationships

  3. Pediatric Ulcerative colitis activity index (PUCAI) [ Time Frame: 16 weeks ]
    Change in Pediatric ulcerative colitis activity index over time

  4. Weighted Pediatric Crohn Disease activity index (wPCDAI) [ Time Frame: 16 weeks ]
    Change in weighted Pediatric Crohn Disease activity index over time

  5. Physician Global Assessment (PGA) Score [ Time Frame: 16 weeks ]
    Change in physician global assessment score over time

  6. Heart Rate Variability (HRV) [ Time Frame: 16 weeks ]
    Evaluating change in HRV from baseline until study completion



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03863704


Contacts
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Contact: Sujay Joseph 516 472 3650 sjoseph37@northwell.edu
Contact: James Markowitz, MD 516 472 3650

Locations
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United States, New York
Steven & Alexandra Cohen Children's Medical Center of New York Recruiting
New Hyde Park, New York, United States, 11042
Contact: Sujay Joseph    516-472-3650    sjoseph37@northwell.edu   
Principal Investigator: Benjamin Sahn, MD         
Sponsors and Collaborators
Northwell Health
Investigators
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Principal Investigator: Benjamin Sahn, MD Steven & Alexandra Cohen Children's Medical Center - Northwell Health
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Responsible Party: Northwell Health
ClinicalTrials.gov Identifier: NCT03863704    
Other Study ID Numbers: 18-0945
First Posted: March 5, 2019    Key Record Dates
Last Update Posted: July 13, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Crohn Disease
Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colitis
Colonic Diseases