Vagal Nerve Stimulation for Intestinal Barrier Dysfunction in Healthy Volunteers

NCT04061564 | Completed Phase 1 DMC

• 1 other identifier: QMERC2018/83
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a proof of concept randomised placebo controlled crossover trial to evaluate the effect of transcutaneous vagal nerve stimulation on a stress model of increased intestinal permeability in healthy human subjects. Intestinal permeability perturbation is a phenomenon which is being increasingly recognised as a contributing factor to a multitude of diseases - including inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). There are currently limited effective treatment methods known to improve this intestinal permeability perturbation and the use of vagal nerve stimulation would present itself as an inexpensive, non-invasive and non-pharmacological method of reversing this dysfunction. Vagal nerve stimulation efficacy in reversing stress related intestinal barrier dysfunction is available from proof of concept animal models. This mechanistic project is an important first step in this field of research and will serve as a basis for further research into the role of vagal nerve stimulation in intestinal barrier dysfunction.

Conditions

Intestinal Barrier Dysfunction

Outcome Measures

Primary Outcomes (1)

• The effect of vagal nerve stimulation on corticotropin releasing hormone induced intestinal barrier dysfunction

  Blood (Intestinal fatty acid binding protein, CD14, Lipopolysaccaride binding protein, dual sugar test result) and urine analyses (the dual sugar test) will be used to determine the intestinal barrier function before and after vagal nerve stimulation. Stress induced intestinal barrier dysfunction will be reproduced with the administration of corticotropin releasing hormone. Intestinal fatty acid binding protein, CD14, Lipopolysaccaride binding protein will be measured quantitatively using the enzyme-linked immunosorbent assay and results will be presented in microgram/litre . Serum and urine sugar concentrations will be measured using high performance liquid chromatography. Results will be presented as a ratio between the monosaccharide and di-saccharide sugar concentrations (i.e. lactulose to rhamnose and lactulose to mannitol ratios).

  2 months

Secondary Outcomes (2)

• The effect of vagal nerve stimulation on autonomic parameter - mean root square difference of RR intervals

  2 months

• The effect of vagal nerve stimulation on autonomic parameter - low frequency to high frequency ratio of RR intervals

  2 months

Study Arms (2)

Active transcutaneous vagal nerve stimulation

ACTIVE COMPARATOR

The participant will be administered vagal nerve stimulation to each ear (20 minutes in total)

Device: Vagal nerve stimulation

Sham transcutaneous vagal nerve stimulation

SHAM COMPARATOR

The participant will be administered sham stimulation to each ear (20 minutes in total)

Device: Vagal nerve stimulation

Interventions

Vagal nerve stimulation DEVICE

The participant will be administered electrical stimulation at a level specifically set to their comfort. This will be performed using a TENS machine device.

Active transcutaneous vagal nerve stimulation; Sham transcutaneous vagal nerve stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy males and females between the ages of 18 - 65
• Participants who are able to give informed consent
• Volunteers should be able to attend the Wingate institute on 2 occasions

You may not qualify if:

• Healthy males and females between the ages of 18 - 65
• Participants who are able to give informed consent
• Volunteers should be able to attend the Wingate institute on 2 occasions
• Past medical history of diabetes (type 1 or 2)
• Past medical history of inflammatory bowel disease, Coeliac disease, a diagnosis of irritable bowel syndrome or significant gastrointestinal symptoms not otherwise medically diagnosed
• Patients actively taking non-steroidal anti-inflammatory medications (NSAIDs) or corticosteroids
• Probiotic or antibiotic intake over the past 3 months
• Pregnant or breast feeding participants
• Participants with known or suspected disorders of the hypothalamo-pituatory axis
• Participants with a history of anaphylaxis
• Chronic disease or any regular medication intake not already specified above; in particular:
• Participants with known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure (CHF);
• Participants with clinically significant abnormal screening 3 lead 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);
• Participants who are 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).

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

The Wigate Institute, Barts and the London School of Medicine and Dentistry

London, N1 1HQ, United Kingdom

Location

MeSH Terms

Interventions

Vagus Nerve Stimulation

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The use of the device in a location which will not stimulate the vagal nerve
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Proof of concept randomised, placebo controlled, single blinded, cross over study

Study Record Dates

• First Submitted: July 18, 2019
• First Posted: August 20, 2019
• Study Start: May 13, 2019
• Primary Completion: August 15, 2019
• Study Completion: September 15, 2019
• Last Updated: March 8, 2022

Record last verified: 2019-07

Locations

GB (1)