Does Improving Vagal Tone Increase Mitochondrial Bioenergetics

Study Overview
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Brief Summary
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This study evaluates the effect of auricular neurostimulation on mitochondrial bioenergetics and inflammation through vagal nerve modulation via non-invasive percutaneous electrical nerve field stimulator in children with functional gastrointestinal disorders.

Detailed Description
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In understanding the pathophysiology of pediatric functional gastrointestinal disorders (FGID), it has been documented that subjects have decreased vagal tone. Vagal tone in turn modulates mitochondrial bioenergetics and plays a role in anti inflammatory effects. Further defining these brain-body connections that underlie FGID's could help guide future treatment. The investigators postulate that a 4 week neuro-stimulation with an Electro Auricular Device that has already shown to increase vagal tone will produce an increase in mitochondrial bioenergetics and decrease in inflammatory markers in this patient group.

Official Title
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Does Improving Vagal Tone Increase Mitochondrial Bioenergetics

Conditions
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Functional Gastrointestinal Disorders, Irritable Bowel Syndrome, Dyspepsia, Functional Abdominal Pain Syndrome

Intervention / Treatment
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* Device: Percutaneous neurostimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English-speaking and able to verbalize their condition and concerns about nausea, pain and other symptoms Subjects will meet Rome IV criteria for functional nausea, irritable bowel syndrome, dyspepsia or functional abdominal pain as determined by a pediatric gastroenterologist Patients must have an intact external ear that is free of infection or severe dermatological conditions, have stable vital signs for their respective age, no history of seizures and no currently implanted electrical device Exclusion Criteria: Mental retardation or pervasive developmental disorder or epilepsy Psychosis Genetic or chromosomal disorders Pregnancy Subjects who admit to substance abuse during screening Patients with findings of peptic ulcer disease, H.pylori gastritis, celiac disease, inflammatory bowel disease, allergic disorders, or any chronic condition or medication that may cause nausea or pain Patients who are treated with opioids or who had any changes in their medical regimen in the past four weeks prior to study Patients with a history of allergy to adhesives

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All subjects will receive the same electro auricular device
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Percutaneous neurostimulation<br>Subjects will have 4 weeks of active therapy. | Device: Percutaneous neurostimulation<br>* Percutaneous neurostimulation using NSS-2 Bridge device<br>* Other names: NSS-2 Bridge by Innovative Health Solutions;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Measure Different Mitochondrial Bioenergetic Markers, Including Basal Respiratory Capacity | Blood draw will be tested for mitochondrial function, including basal respiratory capacity, ATP production and spare respiration and to detect changes in protein which can be an indicator for inflammation. Basal Respiratory Capacity (pmol/min) is better when value is higher. | Baseline, at follow-up visit 4 (Week 4) and at follow up visit 5 (Week 8 or 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Measure Heart Rate Variability | EKG tracing will be used to analyze Heart Rate Variability as an indirect measure of vagal nerve output and central autonomic control. | At date of baseline assessment (beginning of therapy). Also assessed at follow-up visit 4 (Week 4) and 5 (Week 8 or 12) | 
| To Measure Functional Disability Inventory | The Functional Disability Inventory (FDI) questionnaire will be used to assess change in symptoms. Participants will rank physical trouble or difficulty completing 15 different daily activities (Eating regular meals, Being at school all day, Walking up stairs, etc.) on a scale of 0-4. Scale:0-No trouble A little trouble Some Trouble A lot of Trouble Impossible Higher scores (4) indicate more difficulty functioning due to physical health. The total score ranges from 0 to 60 among 15 questions. The individual score for all 15 questions are added together for the total score. If all 15 questions are answered as 0- no trouble then the total score would be 0 (lowest difficulty). If all 15 questions are answered as 4-Impossible, then the total score would be 60 (highest difficulty). An assortment of answers will fall within this 0-60 range depending on the difficulty level answer for each question. | At date of baseline assessment (beginning of therapy). Also assessed at follow-up visit 4 (Week 4) and visit 5 (8 or 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FGID, Neural Stimulation, Functional Abdominal Pain, Dysautonomia