Electrical Vagal Nerve Stimulation in Ulcerative Colitis

NCT03908073 | Terminated DMC FDA Device

• 1 other identifier: 18/LO/1693
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

There are approximately 2.5-3 million patients with inflammatory bowel disease (IBD) across Europe, with associated healthcare costs of €4.6-5.6 billion per annum (1). IBD is associated with a significant reduction in quality of life. Treatments directed towards modifying the inflammatory response, such as anti-tumour necrosis factor-alpha (TNF-α) agents, are expensive, can necessitate admission to hospital for their administration and can be associated with side effects (2 3). Thus, the development of a novel non-pharmacological anti-inflammatory intervention, such as electrical vagal nerve stimulation, is warranted. This is a proof of concept study which aims to investigate whether transcutaneous vagal nerve stimulation is effective at reducing stress induced inflammatory cytokine levels in patients with quiescent ulcerative colitis.

Conditions

Ulcerative Colitis; Vagal Nerve Stimulation; Transcutaneous Vagal Nerve Stimulation

Keywords

Ulcerative Colitis; Vagal Nerve Stimulation; Transcutaneous Vagal Nerve Stimulation; Cytokines; LPS stimulated cytokine production

Outcome Measures

Primary Outcomes (1)

• The effect of active transcutaneous vagal nerve stimulation on LPS stimulated TNF-α production in comparison to sham after the stress protocol

  Whole blood taken from the participants is stimulated with LPS. The concentration of TNF-α will be measured using the ELISA technique. TNF-α level of intervention versus sham is the primary outcome measure.

  1 year

Secondary Outcomes (3)

• The effect of active transcutaneous vagal nerve stimulation compared to sham on LPS stimulated TNF-α production without the stress protocol

  1 year

• Cardiac vagal tone at baseline visits 1 and 2 and post stress protocol

  1 year

• The effect of active transcutaneous vagal nerve stimulation compared to sham on LPS stimulated Il6 and Il10 production with and without the stress protocol

  1 year

Study Arms (2)

Active transcutaneous vagal nerve stimulation

ACTIVE COMPARATOR

The participant will be taught how to use the device and administer doses in our laboratory and independently at home over a period of 24 hours.

Device: Transcutaneous vagal nerve stimulation

Sham transcutaneous vagal nerve stimulation

PLACEBO COMPARATOR

The participant will be taught how to use the device and administer doses in our laboratory and independently at home over a period of 24 hours.

Device: Transcutaneous vagal nerve stimulation

Interventions

Transcutaneous vagal nerve stimulation DEVICE

The use of a transcutaneous vagal nerve stimulator by the participant

Active transcutaneous vagal nerve stimulation; Sham transcutaneous vagal nerve stimulation

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females between 18 and 76 years of age (inclusive).
• Has a clinical diagnosis of UC at least 3 months before screening according to accepted international guidelines.
• Quiescent disease. Disease activity will be assessed using the validated partial Mayo score and faecal calprotectin of \<4 and \<250 μg/g (18) respectively, scored within 3 months of entry into the study. Faecal calprotectin \<250 μg/g within 2 weeks before study entry to confirm that there has been no change in activity status.
• Stable medications regimen for 3 months prior to entry into the study, defined as no additions to UC treatment or dosage escalations.
• Patient is willing and able to participate in the study for the required duration, can understand and is willing to sign the ICF and agrees to undergo all protocol-related tests and procedures.
• Patient has a BMI between 18 and 35 kg/m2 inclusive.

You may not qualify if:

• Has severe extensive colitis and is at imminent risk of colectomy.
• Presence of a stoma or history of a fistula.
• Currently taking any topical or oral corticosteroids.
• Currently taking any anti-TNF therapy, azathioprine, 5-mercaptopurine or methotrexate.
• Is pregnant, lactating or thinking of becoming pregnant during the study period, or of childbearing years and is unwilling to use and accepted form of birth control.
• (Female patients of child-bearing potential must have a negative urine pregnancy test at Screening/pre-dose on Day 1 of the study, excluding female patients of non-child bearing potential who are surgically sterile or post-menopausal. \[To be considered post-menopausal female patients must be without menses for 12 consecutive months before screening\].)
• Patient has unstable acute illness or exacerbation or an unstable chronic illness or chronic disease (other than UC) that may affect assessments for this study as determined by previous physical examination, medical history, vital signs, ECG, and laboratory (serum biochemistry, haematology, urinalysis) assessments. (Note: Non-fasting elevations of cholesterol and triglycerides are not considered clinically significant.)
• Patient with medical history of hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
• Has known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure (CHF);
• Has known or suspected cerebrovascular disease (e.g. prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery);
• Has a clinically significant abnormal screening Electrocardiogram (ECG) e.g. second and third degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction);
• Has had a cervical vagotomy;
• Has uncontrolled high blood pressure (systolic \>160, diastolic \>100 after 3 repeated measurements within 24 hours);
• Is currently implanted with an electrical and/or neurostimulator device (e.g.. cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, cochlear implant, sphenopalatine ganglion stimulator or occipital nerve stimulator);
• Has been implanted with metal cervical spine hardware or has a metallic implant near the gammaCore® stimulation site;

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

Tamara Mogilevski

London, Select One, E1 2AJ, United Kingdom

Location

Related Publications (1)

• Mogilevski T, Hardy MY, Takahashi K, Smith R, Nguyen AL, Farmer A, Lindsay JO, Tye-Din JA, Aziz Q, Gibson PR. Effects of Stress, Vagal Nerve Stimulation and Disease Activity on Circulating Cytokines, Quantified by an Ultrasensitive Technique, in Ulcerative Colitis: A Pilot Study. JGH Open. 2025 Jun 28;9(7):e70206. doi: 10.1002/jgh3.70206. eCollection 2025 Jul.

  PMID: 40584280 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind placebo controlled
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Proof of concept prospective randomized double-blind crossover study evaluating the use of transcutaneous vagal nerve stimulation in a model of acute psychological stress in participants with quiescent Ulcerative colitis

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: April 9, 2019
• Study Start: October 30, 2018
• Primary Completion: March 15, 2021
• Study Completion: March 15, 2021
• Last Updated: March 22, 2022

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)