Does Improving Vagal Tone Increase Mitochondrial Bioenergetics

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.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Irritable Bowel Syndrome; Functional Gastrointestinal Disorders; Functional Abdominal Pain Syndrome
• Intervention / Treatment: Device: Percutaneous neurostimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Percutaneous neurostimulation; Subjects will have 4 weeks of active therapy.	Device: Percutaneous neurostimulation; Percutaneous neurostimulation using NSS-2 Bridge device; Other Names: NSS-2 Bridge by Innovative Health Solutions

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: Gisela Chelimsky, MD, Medical College of Wisconsin

Publications and helpful links

General Publications

• Kovacic K, Hainsworth K, Sood M, Chelimsky G, Unteutsch R, Nugent M, Simpson P, Miranda A. Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.
• He X, Zhao M, Bi X, Sun L, Yu X, Zhao M, Zang W. Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases. Br J Pharmacol. 2015 Dec;172(23):5489-500. doi: 10.1111/bph.13010. Epub 2015 Jan 13.
• Liu Q, Wang EM, Yan XJ, Chen SL. Autonomic functioning in irritable bowel syndrome measured by heart rate variability: a meta-analysis. J Dig Dis. 2013 Dec;14(12):638-46. doi: 10.1111/1751-2980.12092.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 6, 2019
• Primary Completion (ACTUAL): September 24, 2019
• Study Completion (ACTUAL): September 24, 2019

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: April 26, 2019
• First Posted (ACTUAL): April 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Functional Abdominal Pain; Dysautonomia; FGID; Neural Stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease; Signs and Symptoms, Digestive; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Dyspepsia; Irritable Bowel Syndrome; Abdominal Pain; Gastrointestinal Diseases; Digestive System Diseases
• Other Study ID Numbers: 1101710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes