A Study of Auricular Neurostimulation for Children With Cyclic Vomiting Syndrome

March 13, 2026 updated by: Gila Ginzburg, Medical College of Wisconsin

Auricular Neurostimulation for Children With Cyclic Vomiting Syndrome: A Randomized, Sham Controlled Trial

Cyclic vomiting syndrome (CVS) is a fairly common disorder characterized by relentless episodes of vomiting followed by return to baseline health.The majority of children with CVS have concurrent severe abdominal pain and migraine-features, causing significant disability during the attacks. There are very few non-drug treatment options for CVS. Many patients are treated with antidepressants that are often ineffective and may cause serious side effects. Emergency room visits and hospitalizations for patients with CVS is extremely high and the syndrome has an immense impact on quality of life. Safe and effective, non-pharmacological therapies for children with CVS are greatly needed.

Nausea, vomiting and gastrointestinal pain is modulated by the vagus nerve, an important regulator of the autonomic nervous system. The vagus communicates signals between the gastrointestinal tract and the central nervous system. Many studies indicate that vagal nerve stimulation is effective for various pain and vomiting conditions. Recent studies show that vagus nerve signaling is impaired in children with CVS. Researchers have demonstrated safety and efficacy of auricular percutaneous electrical nerve field stimulation (PENFS) targeting the vagus nerve in a small study of children with CVS. The aim of the current study is to investigate the effects of non-invasive PENFS on CVS episode frequency, duration and severity compared to a sham device in a randomized clinical trial.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction characterized by severe, stereotypical and disabling episodes of intense nausea and vomiting, lasting anywhere from 2 hours to 7 days. The disorder is more prevalent than commonly recognized and is estimated to occur in 1.9% of children. The medical costs for the diagnosis and treatment of CVS are immense and quality of life is markedly affected and worse in children with CVS compared to other gut-brain disorders.

About 80% of patients with CVS suffer from concurrent migraine headaches or abdominal migraines during the episodes. Therapies are therefore targeted both towards both nausea and vomiting and aggressive pain control. Therapies are empiric, and response is often variable with numerous patients still requiring Emergency Room visits or hospital admissions. Tricyclic antidepressants are traditionally the most commonly used "off-label" drugs for children with CVS. These drugs may cause serious side effects, and are frequently discontinued due to intolerable adverse effects. Most recent CVS treatment guidelines in fact call for use of these antidepressants only in refractory cases and instead, increased use of non-pharmacological interventions in all children with CVS. Safer and more effective treatments for children with CVS are much needed. Currently, there are no FDA-approved drugs for the treatment of CVS in children.

The mechanisms underlying CVS remain unclear but there is emerging consensus of altered brain-gut neurocircuitry and autonomic nervous system imbalance. Autonomic abnormalities are previously documented in both children and adults with CVS. Researchers have recently demonstrated significantly altered dynamic, cardiac vagal function in children with CVS compared to age and size matched healthy controls, supporting the use of interventions that target vagal signaling.

Interventions targeting the underlying autonomic imbalance such as auricular vagal nerve stimulation are likely targeting the underlying autonomic imbalance via stimulation of the auricular branch of the vagus in the outer ear. The ear is innervated by several cranial nerves including the vagus (CN X) which projects directly to brainstem nausea and vomiting centers. Stress and elevated sympathetic nervous system activity may contribute to initiation of vomiting in CVS patients and therapy via vagal modulation may alter these signals and prevent episodes.

Non-invasive, auricular neurostimulation using the percutaneous electrical nerve field stimulation (PENFS) device has been demonstrated effective for gastrointestinal pain in a randomized, sham controlled clinical trial. More recently, PENFS was demonstrated effective in an open-label, prospective pilot study of 30 children with drug-refractory CVS. There was a significant improvement in both frequency and duration of CVS episodes from baseline (p<0.0001). Notably, a positive effect on quality of life was demonstrated at long-term follow-up after only 6 weeks of therapy. At 6 months follow-up, 80% demonstrated at least 50% improvement in either frequency or duration of episodes with a median response duration of 113 days. Importantly, 100% of these patients were satisfied with the treatment and no serious side effects were reported. Auricular neurostimulation thus modulates autonomic nervous system balance, thereby improving nausea and vomiting presumably by altering vagal signaling with secondary effects of improving quality of life.

The aim of this study is to further investigate the efficacy of auricular neurostimulation using PENFS in a randomized, sham controlled study design in a large cohort of children with CVS. Children ages 5-18 years, evaluated at Children's Wisconsin hospital gastroenterology clinic and meeting formal criteria for CVS based on 2025 NASPGHAN guidelines may be eligible to participate. Subjects will be randomized 2:1 to receive 5 consecutive weeks of active or sham PENFS therapy in a blinded fashion. Subjects will be followed for 12 months after completion of therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Children's Wisconsin
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Episodic vomiting that meet criteria for CVS based on the 2025 NASPGHAN guidelines for diagnosis of pediatric CVS
  • English-speaking
  • Lack of other explanation for vomiting
  • Intact external ear that is free of infection or severe dermatological conditions
  • Stable stable vital signs for their respective age
  • No currently implanted electrical device
  • Family able to accurately describe symptoms and number of vomiting episodes
  • At least 2 vomiting episodes during the 6 months prior to enrollment

Exclusion Criteria:

  • Medically complex children or those who take a medication or suffer from another active disease that explain symptoms
  • Children or their parents who have significant developmental delay
  • Participants diagnosed with alternate conditions that explains their symptoms after undergoing medical workup per standard of care
  • Patients with findings of active disease such as intestinal malrotation, peptic ulcer disease, H.pylori gastritis, celiac disease, inflammatory bowel disease, allergic disorders, hydronephrosis, metabolic disorder or any other active chronic condition or medication that may cause of vomiting
  • Patients who are treated with a new drug affecting the central nervous system in the 4 weeks prior to enrollment
  • Pregnancy
  • Severe cardiopulmonary diseases such as chronic obstructive pulmonary disease (COPD) or coronary artery disease
  • Current chronic marijuana use defined as marijuana use > 2 times per week over the last 6 months prior to study enrollment
  • Previously treated with a PENFS device

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active Percutaneous Electrical Nerve Field Stimulation (PENFS)
Active PENFS device x 5 consecutive weeks
Device: Active percutaneous electrical nerve field stimulation
Auricular vagus nerve stimulation using an percutaneously placed, active device that is worn for 5 days/week for several consecutive weeks
Other Names:
  • IB-stim
Sham Comparator: Sham Percutaneous Electrical Nerve Field Stimulation (PENFS)
Sham PENFS device x 5 consecutive weeks
Device: Sham percutaneous electrical nerve field stimulation
Auricular vagus nerve stimulation using a sham device that is percutaneously placed on the wear and worn for 5 days/week for several consecutive weeks
Other Names:
  • IB-stim

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cyclic Vomiting Syndrome Burden Index
Time Frame: From enrollment (baseline) to 6 months after end of treatment
A 5-item survey assessing the frequency, duration and severity of CVS attacks with scores ranging from minimum 0 to maximum 25 and higher score indicating worse outcome.
From enrollment (baseline) to 6 months after end of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pediatric Migraine Disability Assessment (PedMIDAS)
Time Frame: From enrollment (baseline) to 6 months after end of therapy
8-item questionnaire designed to assess disability associated with migraine conditions. Total score ranges from minimum 0 (no disability) to >50 (severe disability) with higher scores indicating worse outcome.
From enrollment (baseline) to 6 months after end of therapy
Symptom Response Scale
Time Frame: From enrollment (baseline) to 6 months after end of treatment
Assessment of global symptom response based on a 15-point scale with score ranging from minimum -7 to maximum +7 (0=no change). Higher scores indicate improved outcome.
From enrollment (baseline) to 6 months after end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical College of Wisconsin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gila Ginzburg, MD, Medical College of Wisconsin

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 11, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 6, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRO00055846

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified IPD such as patient reported outcome survey data may be shared with other researchers upon request

IPD Sharing Time Frame

End of data collection (12/2028) through following year (12/2029)

IPD Sharing Access Criteria

Other investigators may access de-identified patient reported outcome survey data upon request. Data would be shared if permitted by IRB by exporting de-identfied data from Redcap database.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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