Defining Adolescent Nausea Through Brain Imaging and Neurostimulation Response

Study Overview
=================
Brief Summary
-----------------
This study evaluates the efficacy of auricular neurostimulation via an non-invasive percutaneous electrical nerve field stimulator (PENFS) in adolescents with functional nausea. A neurostimulator is applied to the outer ear and stimulates several nerves that are thought to be involved in transmission of nausea and vomiting signals. Half of the study subjects will receive an active nerve stimulator while the other half will receive an inactive one.

Detailed Description
-----------------
By stimulating branches of several cranial nerves in the outer ear, this study aims to improve symptoms and quality of life in adolescents with functional nausea. The study has the following specific aims: To define adolescent functional nausea into subtypes based on clinical characterization and physiologic testing. Evaluating the efficacy of auricular neurostimulation via PENFS for functional nausea. Subjects will be randomized into two groups: 1) neurostimulation versus 2) sham. They will receive either an active or non-active (sham group) device for 5 days each week x 4 weeks total. Those who do not improve will receive an additional 4 weeks of therapy with active stimulation. Investigate possible brain functional connectivity changes induced by auricular neurostimulation compared to patients with irritable bowel syndrome and healthy controls

Official Title
-----------------
Defining Adolescent Nausea Through Brain-Gut Physiology and Non-Invasive Neurostimulation Response

Conditions
-----------------
Functional Gastrointestinal Disorders

Intervention / Treatment
-----------------
* Device: Active Auricular Neurostimulation
* Device: Sham Auricular Neurostimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Meeting pediatric Rome IV criteria for functional nausea English-speaking and able to verbalize their condition and concerns about nausea, pain and other symptoms Lack of other explanation for symptoms Intact external ear that is free of infection or severe dermatological conditions, - - No currently implanted electrical device Exclusion Criteria: Medically complex and/or suffering from medical condition that may explain symptoms Taking a medication that may explain symptoms Significant developmental delays Patients treated with a new drug affecting the central nervous system within 4 weeks of study start Infection or severe dermatological condition of ear Currently implanted electrical device Patients with a history of severe allergy to adhesives

Ages Eligible for Study
-----------------
Minimum Age: 11 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double blind placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Auricular Neurostimulation<br>Intervention: Active Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks | Device: Active Auricular Neurostimulation<br>* Active auricular neurostimulation for 4 weeks. Subjects in Active group who do not have significant improvement after 4 weeks may receive an additional 4 weeks of active neurostimulation therapy.<br>* Other names: Neuro-Stim System-2;|
| Sham Comparator: Sham Auricular Neurostimulation<br>Intervention: Sham (Inactive) Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks. | Device: Sham Auricular Neurostimulation<br>* Sham auricular neurostimulation for 4 weeks with identical device as the active but lacking the electrical charge. Subjects in Sham group who do not have significant improvement after 4 weeks may receive an additional 4 weeks of active neurostimulation therapy.<br>* Other names: Sham neurostimulation without electrical charge;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea Severity Scale | Measures 1) frequency of nausea on a scale 0-4 over past week (0=not at all; 4=every day), 2) average number of nausea episodes/day over past week on a scale 0-4 (0=none; 4=constant), 3) average duration of nausea episodes over past week on scale 0-4 (0=none; 4=most or all of day) and 4) severity of nausea on scale 0-10 (0=none;10=most nausea possible). The severity subscale is converted to a 5 point scale ranging from 0-4. The mean of all 4 subscales yields a total score ranging from 0 to 4, with a higher score indicating more severity. | Change from baseline Nausea Severity Scale score at 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea Profile | Measures 3 dimensions of nausea (Emotional, GI and Somatic distress) with 17 items. Each sub scale is measured on a 10-point scale from 0-9 (0=not at all; 9=severely). Total score is calculated as follows: actual score/153 * 100%. Subscales are similarly computed into a percentage score. Higher percentage indicates worse outcomes. | Change from baseline total Nausea Profile score at 4 weeks. | 
| Baxter Retching Faces Scale | Measures daily nausea severity on a pictorial faces scale from 0-10 (0=no nausea; 10=most nausea possible). Weekly averages will be computed and change from baseline to average severity during last week of therapy will be assessed. Higher values indicate worse outcome. | Change from baseline Baxter Retching Faces scale score at 4 weeks. |