Crohn DiseaseVNSNCT05165108
Non-invasive Vagus Nerve Stimulation in the Treatment of Crohn's Disease - A Pilot Study
A study testing Vagal Nerve Stimulator in people with Crohn Disease, run by Indiana University at 1 site in United States.
Trial summary
To assess the safety and efficacy of transcutaneous vagal stimulation in adult patients with active Crohn's disease. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Vagal Nerve Stimulator
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2021to 12 Aug 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Crohn's disease diagnosis for at least 3 months, confirmed by clinical, biochemical, and endoscopic evaluations.
- Patients with CD involving the small bowel and / or colon with active symptoms with Crohn's Disease Activity Index (CDAI) > 220 despite at least one conventional therapy (corticosteroids and/or immunosuppressives) with a stable dose will be included.
- Elevated Fecal calprotectin ≥ 200 micro g/g within the past 4 weeks prior to enrollment
- If on corticosteroids, the dose must be stable and ≤ 20mg/day prednisone or equivalent for at least 14 days before entry into study.
- If on background immunosuppressive treatment the dose must be stable with the following parameters:
- 56 days (8 weeks) for Immunomodulators (methotrexate, 6-MP, Azathioprine) and small molecules (upadacitinib)
Show all 10Show fewer
- 112 84 days (16 12 weeks) for biologics (Infliximab, Adalimumab, Vedolizumab, Ustekinumab, another biologic Risankizumab)
- Clinical laboratory evaluations (including a chemistry panel, complete blood count [CBC], and urinalysis [UA]) within the reference range for the test laboratory, unless a typical consequence of CD or deemed not clinically significant by the Investigator.
- Colonoscopy within the previous 1 year with no evidence of colonic dysplasia or cancer.
- 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 pre-stenotic dilatation
- Presence of intra-abdominal or perirectal abscess
- Crohn's Disease Activity Index (CDAI) < 220
- Fistula with clinical or radiological evidence of abscess
- Perianal CD with or without rectal involvement
Show all 19Show fewer
- Ileostomy, colostomy, enteral or parenteral feeding
- Short gut syndrome.
- Clinical condition medically or surgically unstable that, at the discretion of the investigator would not be compatible with the patient's participation in the study
- Any malignant neoplasia, in the year prior to screening ,except for nonmelanoma skin cancer.
- 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 within the past 4 weeks (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
- 18. Participation in any other Investigational drug and/or treatment currently or planned during the length of the study 19. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention 20. Pregnancy or Lactation 21. Comorbid disease with high likelihood of requiring corticosteroid use 22. Inability to comply with study and follow-up procedures 23. Non-English speaking. 24. Known cardiac condition causing or with potential to cause arrhythmia 25. Patients diagnosed with narrowing of the arteries (carotid atherosclerosis) 26. Patients who have had surgery to cut the Vagus nerve in the neck (cervical vagotomy) 27. Patients with clinically significant untreated hypertension, hypotension, bradycardia, or tachycardia.
- 28. Have a metallic device such as a stent, bone plate or bone screw implanted at or near their neck.
- 29. Are using another device at the same time (e.g., TENS Unit, muscle stimulator)
Trial locations and contacts
1 site in 1 country.
About this study
To assess the safety and efficacy of transcutaneous vagal stimulation in adult patients with active Crohn's disease.
Read the detailed description
Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation in the digestive tract. The pathogenesis of IBD involves immunological, genetic and environmental factors. Currently there is no cure for Crohn's disease and available medical and surgical treatments are expensive and often associated with significant side effects. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are widely used for treatment of Crohn's disease. Electrical neuromodulation is a new treatment approach of bioelectronic medicine, involving molecular medicine, neuroscience, and bioengineering. Multiple possible mechanisms have been proposed for electrical neuromodulation in GI diseases, including central, autonomic, and/or enteric mechanisms. Vagal tone is significantly blunted in IBD and is associated with high TNF- α levels. Animal and preliminary human studies have demonstrated that electrical vagal nerve stimulation (VNS), including non-invasive vagal stimulation (nVNS), exerts an anti-inflammatory effect by harnessing the cholinergic anti-inflammatory pathway. In healthy humans nVNS has been shown to decrease tumor necrosis factor-α levels. Invasive VNS has been shown to improve inflammation in preliminary studies in patients with Crohn's disease.
Adult patients with active Crohn's disease will be asked to self-administer transcutaneous vagal nerve stimulation three times per day for 16 weeks. Inflammatory laboratory markers will be compared for each patient against their baseline levels to determine if the intervention helps reduce inflammation cause by their Crohn's disease. Questionnaires will be administered to evaluation their symptoms, and quality of life over the 16 week treatment period.
- Conditions
- Crohn Disease
- Being tested
- Vagal Nerve Stimulator
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagal Nerve StimulatorDevice
Also called GammaCore nVNS
A handheld device which consists of a battery powered portable stimulator with a digital control user interface that controls signal amplitude and two steel contact electrodes will deliver the nVNS electrical stimulation to the cervical Vagus nerve. The device has been approved by the U.S. Food and Drug Administration (FDA) for non-invasive Vagus nerve stimulator therapy for adjunctive use for the prevention and treatment of migraine and cluster headaches in adult patients.
| Study group | Role | What they receive |
|---|---|---|
| Non-Invasive VNS | Experimental | Non-Invasive VNS will decrease inflammation in people with Crohn's disease leading to decrease in inflammatory markers and symptoms of disease. Receives: Device: Vagal Nerve Stimulator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fecal Calprotectin From Baseline to 16 Weeks
This test can identify the level of inflammation in the colon of a person with Crohn's Disease. If a person diagnosed with Crohn's Disease subsequently shows low levels (50 -200 ug/mg) of fecal calprotectin, this means that the inflammation is being controlled, so the treatment regime is working.
Measured: Baseline and 16 weeks
Secondary outcomes (4)
Change in Crohn's Disease Activity Index (CDAI) From Baseline to 16 Weeks
CDAI range is minimum 0 and maximum 450. Zero is best score. Four hundred and fifty is the worst score. Lowering the CDAI score by 70 points or more is the goal for this study. A CDAI score of < or = 150 is considered remission.
Measured: Baseline and 16 Weeks
Change in Serum Cytokine Levels From Baseline to 16 Weeks
Cytokine levels within the blood will be assessed and compared to baseline levels. The cytokines being assayed include C- reactive protein, tumor necrosis factor-alpha, Interferon-gamma, Transforming Growth Factor-beta and Interleukins (IL) - 1, 6, 10, 12, 17, 21, 23. (all cytokines will be presented at pg/mL)
Measured: 16 Weeks
Evaluating Change in HRV From Baseline Until Study Completion.
Heart Rate Variability (HRV)
Measured: 16 Weeks
Change in Insulin Levels After First Stimulation
Serum Insulin levels in the blood will be assessed and compared prior to stimulation, and at 20 minutes and 40 minutes after the stimulation. (presented as mCU/mL)
Measured: Baseline Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2021
- Study start30 Nov 2021
- Primary completion12 Aug 2022
- Study completion12 Aug 2022
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- ElectroCore INC
- Responsible party
- Principal investigator, Sashidhar V. Sagi, Indiana University
- Investigators
- Sashidhar V Sagi, MD, Principal investigator, Indiana UniversityThomas V Nowak, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05165108
- Sponsor's protocol ID
- 10734
- Acronym
- VNS
- Status last verified
- Feb 2025
- First submitted
- 7 Sep 2021
- Last updated
- 6 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: all IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Vagus Nerve Stimulation in the Treatment of Crohn's Disease - A Pilot Study
- ClinicalTrials.gov ID
- NCT05165108
- Acronym / sponsor ID
- VNS / 10734
- Conditions
- Crohn Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- ElectroCore INC
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 12 Aug 2022 (actual)
- Study completion
- 12 Aug 2022 (actual)
- First posted
- 21 Dec 2021 (actual)
- Results
- Posted 6 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and efficacy of transcutaneous vagal stimulation in adult patients with active Crohn's disease.
Detailed description
Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) characterized by chronic inflammation in the digestive tract. The pathogenesis of IBD involves immunological, genetic and environmental factors. Currently there is no cure for Crohn's disease and available medical and surgical treatments are expensive and often associated with significant side effects. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are widely used for treatment of Crohn's disease. Electrical neuromodulation is a new treatment approach of bioelectronic medicine, involving molecular medicine, neuroscience, and bioengineering. Multiple possible mechanisms have been proposed for electrical neuromodulation in GI diseases, including central, autonomic, and/or enteric mechanisms. Vagal tone is significantly blunted in IBD and is associated with high TNF- α levels. Animal and preliminary human studies have demonstrated that electrical vagal nerve stimulation (VNS), including non-invasive vagal stimulation (nVNS), exerts an anti-inflammatory effect by harnessing the cholinergic anti-inflammatory pathway. In healthy humans nVNS has been shown to decrease tumor necrosis factor-α levels. Invasive VNS has been shown to improve inflammation in preliminary studies in patients with Crohn's disease.
Adult patients with active Crohn's disease will be asked to self-administer transcutaneous vagal nerve stimulation three times per day for 16 weeks. Inflammatory laboratory markers will be compared for each patient against their baseline levels to determine if the intervention helps reduce inflammation cause by their Crohn's disease. Questionnaires will be administered to evaluation their symptoms, and quality of life over the 16 week treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non-Invasive VNS | Experimental | Device: Vagal Nerve StimulatorNon-Invasive VNS will decrease inflammation in people with Crohn's disease leading to decrease in inflammatory markers and symptoms of disease. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Crohn's disease diagnosis for at least 3 months, confirmed by clinical, biochemical, and endoscopic evaluations.
- Patients with CD involving the small bowel and / or colon with active symptoms with Crohn's Disease Activity Index (CDAI) > 220 despite at least one conventional therapy (corticosteroids and/or immunosuppressives) with a stable dose will be included.
- Elevated Fecal calprotectin ≥ 200 micro g/g within the past 4 weeks prior to enrollment
- If on corticosteroids, the dose must be stable and ≤ 20mg/day prednisone or equivalent for at least 14 days before entry into study.
- If on background immunosuppressive treatment the dose must be stable with the following parameters:
Key exclusion criteria (19 listed)
- Expectation to increase corticosteroids and/or immunosuppressive treatment
- Presence of bowel stricture with pre-stenotic dilatation
- Presence of intra-abdominal or perirectal abscess
- Crohn's Disease Activity Index (CDAI) < 220
- Fistula with clinical or radiological evidence of abscess
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 |
|---|---|---|
| Vagal Nerve StimulatorAlso: GammaCore nVNSA handheld device which consists of a battery powered portable stimulator with a digital control user interface that controls signal amplitude and two steel contact electrodes will deliver the nVNS electrical stimulation to the cervical Vagus nerve. The device has been approved by the U.S. Food and Drug Administration (FDA) for non-invasive Vagus nerve stimulator therapy for adjunctive use for the prevention and treatment of migraine and cluster headaches in adult patients. | Device | Non-Invasive VNS |
Primary outcome
Change in Fecal Calprotectin From Baseline to 16 Weeks
Time frame: Baseline and 16 weeks
This test can identify the level of inflammation in the colon of a person with Crohn's Disease. If a person diagnosed with Crohn's Disease subsequently shows low levels (50 -200 ug/mg) of fecal calprotectin, this means that the inflammation is being controlled, so the treatment regime is working.
4 secondary outcomes
Change in Crohn's Disease Activity Index (CDAI) From Baseline to 16 Weeks
Time frame: Baseline and 16 Weeks
Change in Serum Cytokine Levels From Baseline to 16 Weeks
Time frame: 16 Weeks
Evaluating Change in HRV From Baseline Until Study Completion.
Time frame: 16 Weeks
Change in Insulin Levels After First Stimulation
Time frame: Baseline Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. all IPD that underlie results in a publication
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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.
Sashidhar V Sagi, MD principal investigator
Indiana University
Thomas V Nowak, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vagal Nerve Stimulator in people with Crohn Disease, run by Indiana University 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 10 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: stopped early, as of the sponsor's last update on 6 Mar 2025. 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. 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?
Yes. Results are posted in the registry (first posted 6 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Fecal Calprotectin From Baseline to 16 Weeks (time frame: Baseline and 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Mar 2025.