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Transcutaneous VNS to Treat Pediatric IBD (STIMIBD)

Primary Purpose

Crohn Disease, Ulcerative Colitis

Status

Active

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Transcutaneous Electrical Nerve Stimulation (TENS)

About this trial

This is an interventional treatment trial for Crohn Disease

Eligibility Criteria

10 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
- 28 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:
- 56 days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine)
- 112 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.

Exclusion Criteria:

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
Comorbid disease with high likelihood of requiring corticosteroid use
Inability to comply with study and follow-up procedures
Non-English speaking
Known cardiac condition causing or with potential to cause arrhythmia

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Sham Comparator

Other

Arm Label

nerve stimulation ear then leg

nerve stimulation leg then ear

Subjects receiving Infliximab

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

Fecal Calprotectin

Change in fecal calprotectin over time

Secondary Outcome Measures

Change in Whole blood stimulated cytokine levels over time

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

Patient Reported Outcome (PRO)

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

Pediatric Ulcerative colitis activity index (PUCAI)

Change in Pediatric ulcerative colitis activity index over time

Weighted Pediatric Crohn Disease activity index (wPCDAI)

Change in weighted Pediatric Crohn Disease activity index over time

Physician Global Assessment (PGA) Score

Change in physician global assessment score over time

Heart Rate Variability (HRV)

Evaluating change in HRV from baseline until study completion

Full Information

NCT ID

NCT03863704

First Posted

February 14, 2019

Last Updated

March 6, 2023

Sponsor

Northwell Health

1. Study Identification

Unique Protocol Identification Number

NCT03863704

Brief Title

Transcutaneous VNS to Treat Pediatric IBD

Acronym

STIMIBD

Official Title

Transcutaneous Vagal Nerve Stimulation to Treat Pediatric Inflammatory Bowel Disease

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 14, 2019 (Actual)

Primary Completion Date

December 31, 2022 (Actual)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northwell Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Crohn Disease, Ulcerative Colitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

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.

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

nerve stimulation ear then leg

Arm Type

Sham Comparator

Arm Description

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

Arm Title

nerve stimulation leg then ear

Arm Type

Sham Comparator

Arm Description

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

Arm Title

Subjects receiving Infliximab

Arm Type

Other

Arm Description

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.

Intervention Type

Device

Intervention Name(s)

Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Description

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

Primary Outcome Measure Information:

Title

Fecal Calprotectin

Description

Change in fecal calprotectin over time

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

Change in Whole blood stimulated cytokine levels over time

Description

Time Frame

16 weeks

Title

Patient Reported Outcome (PRO)

Description

Time Frame

16 weeks

Title

Pediatric Ulcerative colitis activity index (PUCAI)

Description

Change in Pediatric ulcerative colitis activity index over time

Time Frame

16 weeks

Title

Weighted Pediatric Crohn Disease activity index (wPCDAI)

Description

Change in weighted Pediatric Crohn Disease activity index over time

Time Frame

16 weeks

Title

Physician Global Assessment (PGA) Score

Description

Change in physician global assessment score over time

Time Frame

16 weeks

Title

Heart Rate Variability (HRV)

Description

Evaluating change in HRV from baseline until study completion

Time Frame

16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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: 28 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: 56 days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine) 112 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. Exclusion Criteria: 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 Comorbid disease with high likelihood of requiring corticosteroid use Inability to comply with study and follow-up procedures Non-English speaking Known cardiac condition causing or with potential to cause arrhythmia

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Benjamin Sahn, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

New Hyde Park

State/Province

New York

ZIP/Postal Code

11042

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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