Crohn DiseaseSTIMIBDNCT03863704
Transcutaneous VNS to Treat Pediatric IBD
A study testing Transcutaneous Electrical Nerve Stimulation (TENS) in people with Crohn Disease and Ulcerative Colitis, run by Northwell Health at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 10 to 21 years
- Conditions the study is for
- Crohn Disease, Ulcerative Colitis
- What is being tested?
- Transcutaneous Electrical Nerve Stimulation (TENS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2019to 31 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Steven & Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11042
About this study
Official title: Transcutaneous Vagal Nerve Stimulation to Treat Pediatric Inflammatory Bowel Disease
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
- Being tested
- Transcutaneous Electrical Nerve Stimulation (TENS)
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Electrical Nerve Stimulation (TENS)Device
To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: Device: Transcutaneous Electrical Nerve Stimulation (TENS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fecal Calprotectin
Change in fecal calprotectin over time
Measured: 16 weeks
Secondary outcomes (6)
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
Measured: 16 weeks
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
Measured: 16 weeks
Pediatric Ulcerative colitis activity index (PUCAI)
Change in Pediatric ulcerative colitis activity index over time
Measured: 16 weeks
Weighted Pediatric Crohn Disease activity index (wPCDAI)
Change in weighted Pediatric Crohn Disease activity index over time
Measured: 16 weeks
Physician Global Assessment (PGA) Score
Change in physician global assessment score over time
Measured: 16 weeks
Heart Rate Variability (HRV)
Evaluating change in HRV from baseline until study completion
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start14 Feb 2019
- Primary completion31 Dec 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin Sahn, MD, Principal investigator, Steven & Alexandra Cohen Children's Medical Center - Northwell Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03863704
- Sponsor's protocol ID
- 18-0945
- Acronym
- STIMIBD
- Status last verified
- Sep 2024
- First submitted
- 14 Feb 2019
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 37849000
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcutaneous Vagal Nerve Stimulation to Treat Pediatric Inflammatory Bowel Disease
- ClinicalTrials.gov ID
- NCT03863704
- Acronym / sponsor ID
- STIMIBD / 18-0945
- Conditions
- Crohn Disease, Ulcerative Colitis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 14 Feb 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| nerve stimulation ear then leg | Sham comparator | Device: Transcutaneous Electrical Nerve Stimulation (TENS)Subjects in this arm will be randomized to receive nerve stimulation with TENS of the ear followed by leg stimulation |
| nerve stimulation leg then ear | Sham comparator | Device: Transcutaneous Electrical Nerve Stimulation (TENS)Subjects in this arm will be randomized to receive leg nerve stimulation with TENS followed by ear nerve stimulation |
| Subjects receiving Infliximab | Other | Device: Transcutaneous Electrical Nerve Stimulation (TENS)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. |
Who may qualify
- Ages
- 10 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous Electrical Nerve Stimulation (TENS)To apply transcutaneous electrical stimulation using a TENS unit to the ear or the leg. | Device | Subjects receiving Infliximab, nerve stimulation ear then leg, nerve stimulation leg then ear |
Primary outcome
Fecal Calprotectin
Time frame: 16 weeks
Change in fecal calprotectin over time
6 secondary outcomes
Change in Whole blood stimulated cytokine levels over time
Time frame: 16 weeks
Patient Reported Outcome (PRO)
Time frame: 16 weeks
Pediatric Ulcerative colitis activity index (PUCAI)
Time frame: 16 weeks
Weighted Pediatric Crohn Disease activity index (wPCDAI)
Time frame: 16 weeks
Physician Global Assessment (PGA) Score
Time frame: 16 weeks
Heart Rate Variability (HRV)
Time frame: 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Derived from this study: PubMed 37849000Sahn 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Sahn, MD principal investigator
Steven & Alexandra Cohen Children's Medical Center - Northwell Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Electrical Nerve Stimulation (TENS) in people with Crohn Disease and Ulcerative Colitis, run by Northwell Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fecal Calprotectin (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03863704, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.