Transcutaneous VNS to Treat Pediatric IBD

NCT ID: NCT03863704

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-14
• Study Completion Date: 2023-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: SHAM_COMPARATOR

Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Type: DEVICE

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

nerve stimulation leg then ear

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

Group Type: SHAM_COMPARATOR

Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Type: DEVICE

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.

Group Type: OTHER

Transcutaneous Electrical Nerve Stimulation (TENS)

Intervention Type: DEVICE

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

Interventions

Transcutaneous Electrical Nerve Stimulation (TENS)

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

Intervention Type: DEVICE

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin Sahn, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

New Hyde Park, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37849000 (View on PubMed)

Other Identifiers

18-0945

Identifier Type: -

Identifier Source: org_study_id