Functional Gastrointestinal DisordersNCT03675321
Defining Adolescent Nausea Through Brain Imaging and Neurostimulation Response
A study testing Active Auricular Neurostimulation in people with Functional Gastrointestinal Disorders, run by Medical College of Wisconsin at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 11 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Functional Gastrointestinal Disorders
- What is being tested?
- Active Auricular Neurostimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 109 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2018to 28 Feb 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 11 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Defining Adolescent Nausea Through Brain-Gut Physiology and Non-Invasive Neurostimulation Response
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.
Read the 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
- Conditions
- Functional Gastrointestinal Disorders
- Being tested
- Active Auricular Neurostimulation, Sham Auricular Neurostimulation
- Medical subject headings
- Gastrointestinal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Auricular NeurostimulationDevice
Also called Percutaneous Electrical Nerve Field Stimulation (PENFS), Neuro-Stim System-2
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.
Sham Auricular NeurostimulationDevice
Also called Sham neurostimulation without electrical charge
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.
| Study group | Role | What they receive |
|---|---|---|
| Auricular Neurostimulation | Experimental | Intervention: Active Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks Receives: Device: Active Auricular Neurostimulation |
| Sham Auricular Neurostimulation | Sham comparator | Intervention: Sham (Inactive) Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks. Receives: Device: Sham Auricular Neurostimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 4 weeks of therapy
Secondary outcomes (2)
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.
Measured: After 4 weeks of therapy
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.
Measured: Average score during week 4 of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2018
- Study start23 Apr 2018
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Functional Gastrointestinal DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, double blind placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katja Karrento, Medical College of Wisconsin
- Investigators
- Katja Kovacic, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03675321
- Sponsor's protocol ID
- 1064187-2
- Other IDs
- 1K23DK116969-01
- Status last verified
- Nov 2025
- First submitted
- 8 May 2018
- Last updated
- 20 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Babygirija R, Sood M, Kannampalli P, Sengupta JN, Miranda A. Percutaneous electrical nerve field stimulation modulates central pain pathways and attenuates post-inflammatory visceral and somatic hyperalgesia in rats. Neuroscience. 2017 Jul 25;356:11-21. doi: 10.1016/j.neuroscience.2017.05.012. Epub 2017 May 17.
PubMed 28526575Roberts A, Sithole A, Sedghi M, Walker CA, Quinn TM. Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. Med Devices (Auckl). 2016 Nov 3;9:389-393. doi: 10.2147/MDER.S107426. eCollection 2016.
PubMed 27843360Kovacic 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.
PubMed 28826627
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Defining Adolescent Nausea Through Brain-Gut Physiology and Non-Invasive Neurostimulation Response
- ClinicalTrials.gov ID
- NCT03675321
- Acronym / sponsor ID
- 1064187-2
- Conditions
- Functional Gastrointestinal Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 23 Apr 2018 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 18 Sep 2018 (actual)
- Results
- Posted 12 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, double blind placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Auricular Neurostimulation | Experimental | Device: Active Auricular NeurostimulationIntervention: Active Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks |
| Sham Auricular Neurostimulation | Sham comparator | Device: Sham Auricular NeurostimulationIntervention: Sham (Inactive) Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks. |
Who may qualify
- Ages
- 11 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Auricular NeurostimulationAlso: Percutaneous Electrical Nerve Field Stimulation (PENFS), Neuro-Stim System-2Active 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. | Device | Auricular Neurostimulation |
| Sham Auricular NeurostimulationAlso: Sham neurostimulation without electrical chargeSham 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. | Device | Sham Auricular Neurostimulation |
Primary outcome
Nausea Severity Scale
Time frame: After 4 weeks of therapy
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.
2 secondary outcomes
Nausea Profile
Time frame: After 4 weeks of therapy
Baxter Retching Faces Scale
Time frame: Average score during week 4 of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28526575Babygirija R, Sood M, Kannampalli P, Sengupta JN, Miranda A. Percutaneous electrical nerve field stimulation modulates central pain pathways and attenuates post-inflammatory visceral and somatic hyperalgesia in rats. Neuroscience. 2017 Jul 25;356:11-21. doi: 10.1016/j.neuroscience.2017.05.012. Epub 2017 May 17.
- Background: PubMed 27843360Roberts A, Sithole A, Sedghi M, Walker CA, Quinn TM. Minimal adverse effects profile following implantation of periauricular percutaneous electrical nerve field stimulators: a retrospective cohort study. Med Devices (Auckl). 2016 Nov 3;9:389-393. doi: 10.2147/MDER.S107426. eCollection 2016.
- Results publication: PubMed 28826627Kovacic 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katja Kovacic, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Auricular Neurostimulation in people with Functional Gastrointestinal Disorders, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nausea Severity Scale (time frame: After 4 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03675321, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.