Cyclic Vomiting SyndromeNCT03434652
Auricular Neurostimulation for Cyclic Vomiting Syndrome
A study testing Percutaneous neurostimulation in people with Cyclic Vomiting Syndrome and Abdominal Migraine, 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 in children and adults with cyclic vomiting syndrome. Read more about this study
- Who is it for?
- Ages 8 to 65 years
- Conditions the study is for
- Cyclic Vomiting Syndrome, Abdominal Migraine
- What is being tested?
- Percutaneous neurostimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2018to 3 Mar 2021
- 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 8 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Meeting Rome IV Pediatric or Adult criteria for Cyclic Vomiting Syndrome (CVS)
- Concurrent abdominal pain with CVS cycle
- English-speaking
- Lack of other explanation for symptoms
- Either predictable, 'calendar-timed' episodes or prodromal symptoms for 12-24 hours that are predictive of episodes onset
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 one week of enrollment
- Infection or severe dermatological condition of ear
- Stable vital signs
- No currently implanted electrical device
- For adults (and adolescents as applicable): pregnancy, severe cardiopulmonary disease, concurrent chronic marijuana use (>2 times/month over past 6 months prior to enrollment)
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: Efficacy of Auricular Neurostimulation for Children and Adults With Cyclic Vomiting Syndrome: a Pilot Study
This study evaluates the efficacy of auricular neurostimulation via an non-invasive percutaneous electrical nerve field stimulator in children and adults with cyclic vomiting syndrome.
Read the detailed description
Cyclic vomiting syndrome (CVS) is an difficult to treat and debilitating functional gastrointestinal disorder presenting with episodes of severe nausea and vomiting. Majority of children and adults with CVS have concurrent severe abdominal pain and migraine-features, rendering them incapacitated during the vomiting cycle.
The vagus nerve carries signals of nausea, vomiting and pain between the brain and the gastrointestinal tract and is part of the autonomic nervous system. The autonomic nervous system appears to be in imbalance in patients with CVS during a vomiting cycle. By stimulating a branch of the vagus nerve in the outer ear, this study aims to improve symptoms and quality of life in both children and adults with CVS.
Subjects in Acute treatment arm will be randomized to receive active vs sham (non-active) neurostimulation therapy for 5 days at the onset of a CVS cycle (1st illness period). They will then cross over to the other group (active vs sham) at the onset of the next CVS cycle (2nd illness period). Subjects in a separate Chronic (Prophylactic) treatment arm receive 6 consecutive weeks of active neurostimulation therapy (5 days/week). Pain, nausea, vomiting, anxiety, quality of life, potential side effects and overall symptom improvement will be monitored before and after therapy.
- Conditions
- Cyclic Vomiting Syndrome, Abdominal Migraine
- Being tested
- Percutaneous neurostimulation
- Medical subject headings
- Familial cyclic vomiting syndrome, Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Percutaneous neurostimulationDevice
Also called Neuro-Stim System (NSS)-2 BRIDGE
Auricular percutaneous neurostimulation
| Study group | Role | What they receive |
|---|---|---|
| Acute therapy: active vs sham percutaneous neurostimulation | Sham comparator | Subject randomized to 5 days of active or sham neurostimulation therapy during the first illness cycle. With the second illness cycle, each subject will then cross over to the other therapy (active or sham). Receives: Device: Percutaneous neurostimulation |
| Chronic therapy: active (open-label) percutaneous neurostimulation | Experimental | Each subject receives 6 consecutive weeks of active (open-label) neurostimulation therapy. Receives: Device: Percutaneous neurostimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rhodes Index of Nausea, Vomiting & Retching (INVR)
Acute therapy arm: Daily nausea and vomiting severity assessed by validated scale 0-32 (0=no symptoms; 32=worse possible nausea/vomiting) with higher scores indicating worse outcomes (greater nausea/vomiting). Daily scores for baseline (day 1) and end of therapy (day 7) were compared for both active and sham groups.
Chronic therapy arm: Daily nausea and vomiting severity assessed by validated scale 0-32 (0=no symptoms; 32=worse possible nausea/vomiting) with higher scores indicating worse outcomes (greater nausea/vomiting). Daily scores were averaged for each week of the 6 weeks of therapy and compared between a baseline assessment and week 6 of therapy.
Measured: Acute arm: at the start of the first and second illness cycle through next 7 days for each illness cycle (active and sham therapy). Chronic arm: from date of baseline assessment (therapy start date) through 6 weeks of therapy.
Secondary outcomes (6)
Numeric Pain Scale
Daily pain severity assessed by numeric pain scale 0-10 (0=no pain; 10=worst possible pain) with higher scores indicating worse outcome (greater pain).
Measured: From date of baseline assessment (therapy start date) through next 7 days for each cycle of therapy with day 7 reported as end of therapy.
Anxiety
State-Trait Anxiety Inventory for Children and Adults. State and trait anxiety is assessed by a validated instrument (raw score 20=minimum anxiety; 60=maximum anxiety) with higher scores indicating worse outcomes (greater anxiety). Scores are covered to standardized T scores (mean 50; standard deviation 10).
Measured: From date of baseline assessment (therapy start date) to end of therapy. For Chronic therapy arm, end of therapy= 6 weeks. For Acute therapy arm, end of therapy = day 7 (on site).
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life
Patient Reported Outcomes Measurement Information Systems (PROMIS). Quality-of-life outcome measure that assesses physical, emotional and psychosocial functioning across six domains (Physical function, Anxiety, Fatigue, Pain Interference). Raw score 37= maximum/best quality of life; raw score 185= minimum/worst quality of life. Scores are covered to standardized T scores (mean 50; SD 10). A lower score indicates improved quality of life.
Measured: From date of baseline assessment (therapy start date) to end of therapy and at 3 months follow-up. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = day 7.
Functional Disability Inventory- Disability in Children
Functional Disability Inventory. A 15-item self-report measure of the degree that children experience difficulty in physical and psychosocial functioning due to impaired physical health. Higher scores indicates worse outcomes (0=minimal disability; 60=maximum disability) and worse disability.
Measured: From date of baseline assessment (therapy start date) to end of therapy and 3 months follow-up. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = 7 days.
Disability in Adults
Sheehan Disability Scale assessing disability and impairment on a scale 0-10 with higher scores indicating more disability. Three sub scales: 1) school/work, 2) social life and 3) family life are assessed (scale 0-10) with a total score reflecting the sum of the 3 subscales (total score range 0-30 with higher score indicating more disability).
No data collected as no adult participants enrolled.
Measured: Anticipated assessment from date of baseline assessment (therapy start date) and end of therapy for each cycle of therapy as well as follow-up visit after end of therapy. However, no adult participants were enrolled.
Symptom Response Scale
Global symptom improvement scale, score ranging from -7 to +7 (0=no change, positive score indicates improvement while negative score indicates worsening).
Measured: From date of baseline assessment (therapy start date) to global symptom assessment at end of therapy. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = 7 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2018
- Study start31 Jan 2018
- Primary completion3 Mar 2021
- Study completion3 Mar 2021
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 (5)Papers the sponsor has linked to this study.
- Other trials for Cyclic Vomiting SyndromeStudies 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
- Crossover
- Model description
- Arm 1 (Acute treatment): Each subject randomized to active vs sham therapy during 1st illness cycle after enrollment, then cross over to the other (active vs sham) during the 2nd illness cycle. Arm 2 (Chronic treatment): Active, chronic (prophylactic) therapy (open label) x 6 consecutive weeks of intervention.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 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
- NCT03434652
- Sponsor's protocol ID
- 1102505-4
- Status last verified
- Jan 2026
- First submitted
- 1 Feb 2018
- Last updated
- 13 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
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.
PubMed 28826627Babygirija 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 28526575Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018;44(1):56-63. doi: 10.1080/00952990.2017.1295459. Epub 2017 Mar 16.
PubMed 28301217Roberts 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 27843360Karrento K, Zhang L, Conley W, Qazi Z, Venkatesan T, Simpson P, Li BUK. Percutaneous electrical nerve field stimulation improves comorbidities in children with cyclic vomiting syndrome. Front Pain Res (Lausanne). 2023 Jun 14;4:1203541. doi: 10.3389/fpain.2023.1203541. eCollection 2023.
PubMed 37389229
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Auricular Neurostimulation for Children and Adults With Cyclic Vomiting Syndrome: a Pilot Study
- ClinicalTrials.gov ID
- NCT03434652
- Acronym / sponsor ID
- 1102505-4
- Conditions
- Cyclic Vomiting Syndrome, Abdominal Migraine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 31 Jan 2018 (actual)
- Primary completion
- 3 Mar 2021 (actual)
- Study completion
- 3 Mar 2021 (actual)
- First posted
- 15 Feb 2018 (actual)
- Results
- Posted 13 Feb 2026
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 in children and adults with cyclic vomiting syndrome.
Detailed description
Cyclic vomiting syndrome (CVS) is an difficult to treat and debilitating functional gastrointestinal disorder presenting with episodes of severe nausea and vomiting. Majority of children and adults with CVS have concurrent severe abdominal pain and migraine-features, rendering them incapacitated during the vomiting cycle.
The vagus nerve carries signals of nausea, vomiting and pain between the brain and the gastrointestinal tract and is part of the autonomic nervous system. The autonomic nervous system appears to be in imbalance in patients with CVS during a vomiting cycle. By stimulating a branch of the vagus nerve in the outer ear, this study aims to improve symptoms and quality of life in both children and adults with CVS.
Subjects in Acute treatment arm will be randomized to receive active vs sham (non-active) neurostimulation therapy for 5 days at the onset of a CVS cycle (1st illness period). They will then cross over to the other group (active vs sham) at the onset of the next CVS cycle (2nd illness period). Subjects in a separate Chronic (Prophylactic) treatment arm receive 6 consecutive weeks of active neurostimulation therapy (5 days/week). Pain, nausea, vomiting, anxiety, quality of life, potential side effects and overall symptom improvement will be monitored before and after therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Arm 1 (Acute treatment): Each subject randomized to active vs sham therapy during 1st illness cycle after enrollment, then cross over to the other (active vs sham) during the 2nd illness cycle. Arm 2 (Chronic treatment): Active, chronic (prophylactic) therapy (open label) x 6 consecutive weeks of intervention.
| Arm | Type | Receives |
|---|---|---|
| Acute therapy: active vs sham percutaneous neurostimulation | Sham comparator | Device: Percutaneous neurostimulationSubject randomized to 5 days of active or sham neurostimulation therapy during the first illness cycle. With the second illness cycle, each subject will then cross over to the other therapy (active or sham). |
| Chronic therapy: active (open-label) percutaneous neurostimulation | Experimental | Device: Percutaneous neurostimulationEach subject receives 6 consecutive weeks of active (open-label) neurostimulation therapy. |
Who may qualify
- Ages
- 8 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Meeting Rome IV Pediatric or Adult criteria for Cyclic Vomiting Syndrome (CVS)
- Concurrent abdominal pain with CVS cycle
- English-speaking
- Lack of other explanation for symptoms
- Either predictable, 'calendar-timed' episodes or prodromal symptoms for 12-24 hours that are predictive of episodes onset
Key exclusion criteria (8 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 one week of enrollment
- 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 |
|---|---|---|
| Percutaneous neurostimulationAlso: Neuro-Stim System (NSS)-2 BRIDGEAuricular percutaneous neurostimulation | Device | Acute therapy: active vs sham percutaneous neurostimulation, Chronic therapy: active (open-label) percutaneous neurostimulation |
Primary outcome
Rhodes Index of Nausea, Vomiting & Retching (INVR)
Time frame: Acute arm: at the start of the first and second illness cycle through next 7 days for each illness cycle (active and sham therapy). Chronic arm: from date of baseline assessment (therapy start date) through 6 weeks of therapy.
Acute therapy arm: Daily nausea and vomiting severity assessed by validated scale 0-32 (0=no symptoms; 32=worse possible nausea/vomiting) with higher scores indicating worse outcomes (greater nausea/vomiting). Daily scores for baseline (day 1) and end of therapy (day 7) were compared for both active and sham groups. Chronic therapy arm: Daily nausea and vomiting severity assessed by validated scale 0-32 (0=no symptoms; 32=worse possible nausea/vomiting) with higher scores indicating worse outcomes (greater nausea/vomiting). Daily scores were averaged for each week of the 6 weeks of therapy and compared between a baseline assessment and week 6 of therapy.
6 secondary outcomes
Numeric Pain Scale
Time frame: From date of baseline assessment (therapy start date) through next 7 days for each cycle of therapy with day 7 reported as end of therapy.
Anxiety
Time frame: From date of baseline assessment (therapy start date) to end of therapy. For Chronic therapy arm, end of therapy= 6 weeks. For Acute therapy arm, end of therapy = day 7 (on site).
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life
Time frame: From date of baseline assessment (therapy start date) to end of therapy and at 3 months follow-up. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = day 7.
Functional Disability Inventory- Disability in Children
Time frame: From date of baseline assessment (therapy start date) to end of therapy and 3 months follow-up. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = 7 days.
Disability in Adults
Time frame: Anticipated assessment from date of baseline assessment (therapy start date) and end of therapy for each cycle of therapy as well as follow-up visit after end of therapy. However, no adult participants were enrolled.
Symptom Response Scale
Time frame: From date of baseline assessment (therapy start date) to global symptom assessment at end of therapy. For Chronic therapy arm, end of therapy = 6 weeks. For Acute therapy arm, end of therapy = 7 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: 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.
- 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 28301217Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018;44(1):56-63. doi: 10.1080/00952990.2017.1295459. Epub 2017 Mar 16.
- 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.
- Derived from this study: PubMed 37389229Karrento K, Zhang L, Conley W, Qazi Z, Venkatesan T, Simpson P, Li BUK. Percutaneous electrical nerve field stimulation improves comorbidities in children with cyclic vomiting syndrome. Front Pain Res (Lausanne). 2023 Jun 14;4:1203541. doi: 10.3389/fpain.2023.1203541. eCollection 2023.
- 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 Percutaneous neurostimulation in people with Cyclic Vomiting Syndrome and Abdominal Migraine, 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 5 inclusion and 8 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 13 Feb 2026. 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 13 Feb 2026). 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?
Rhodes Index of Nausea, Vomiting & Retching (INVR) (time frame: Acute arm: at the start of the first and second illness cycle through next 7 days for each illness cycle (active and sham therapy). Chronic arm: from date of baseline assessment (therapy start date) through 6 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 NCT03434652, which also lists 5 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 13 Feb 2026.