CompletedNCT03434652Updated Feb 13, 2026Results posted

Auricular Neurostimulation for Cyclic Vomiting Syndrome

An interventional study of Percutaneous neurostimulation in Cyclic Vomiting Syndrome and Abdominal Migraine, sponsored by Medical College of Wisconsin. Completed at 1 site in United States. Open to participants aged 8 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-02-13.

Sponsored by Medical College of Wisconsin · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 47
Allocation: Randomized
Ages: 8 Years to 65 Years
Sex: All

Study 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 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 studied

Cyclic Vomiting Syndrome
Abdominal Migraine

Browse trials for

Migraine Disorders 1,521

Who can participate

Ages eligible: 8 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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

Exclusion criteria

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 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)

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 47 participants (actual)

Study arms

Sham comparator
Acute therapy: active vs sham percutaneous neurostimulation
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).
Device: Percutaneous neurostimulation
Experimental
Chronic therapy: active (open-label) percutaneous neurostimulation
Each subject receives 6 consecutive weeks of active (open-label) neurostimulation therapy.
Device: Percutaneous neurostimulation

Interventions

DevicePercutaneous neurostimulation
Auricular percutaneous neurostimulation
Also known as: Neuro-Stim System (NSS)-2 BRIDGE

What researchers measure

Primary outcomes

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.
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.

Secondary outcomes

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).
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
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).
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
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.
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
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.
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
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.
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
Global symptom improvement scale, score ranging from -7 to +7 (0=no change, positive score indicates improvement while negative score indicates worsening).
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

Posted Feb 13, 2026

Participant flow

Participant flow — Overall Study
Milestone	Acute Therapy: Cross-over Active Neurostimulation	Acute Therapy: Cross-over Sham Neurostimulation	Chronic Therapy: Active (Open-label) Neurostimulation
Started	8	7	32
Completed	5	5	30
Not completed	3	2	2
Withdrew: Lost to follow-up	2	2	1
Withdrew: Physician decision	1	0	1

Outcome measures

PrimaryRhodes 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.

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.
Reported as:: Mean · score on a scale

Rhodes Index of Nausea, Vomiting & Retching (INVR)
score on a scale	Acute Therapy Arm: Active Neurostimulation	Acute Therapy Arm: Sham Neurostimulation	Chronic Therapy Arm
Baseline INVR	3.25 ± 3.95	5.80 ± 9.17	10.43 ± 9.78
End of therapy INVR	0.75 ± 1.50	1.50 ± 3.00	2.31 ± 3.88

SecondaryNumeric 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).

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.
Reported as:: Mean · score on a scale

Numeric Pain Scale
score on a scale	Acute Therapy: Active	Acute Therapy: Sham	Chronic Therapy Arm
Baseline	4 ± 0	4.7 ± 3.4	—
End of therapy	1 ± 1	1.3 ± 1.2	—

SecondaryAnxiety

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).

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).
Reported as:: Median · score on STAI state anxiety scale

Anxiety
score on STAI state anxiety scale	Chronic Therapy: Arm 2	Acute Therapy; Active	Acute Therapy: Sham
Baseline	63.5 (52 to 70)	28 (25 to 36)	29 (26 to 34.5)
End of therapy	51 (44 to 54)	—	—
Follow-up	49 (44 to 54)	23.5 (22.5 to 26.5)	36 (30 to 42)

SecondaryPatient 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.

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.
Reported as:: Median · score on a scale

Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life
score on a scale	Chronic Therapy: Arm 2	Acute Therapy: Active	Acute Therapy; Sham
Physical Function: Baseline	25.4 (22.8 to 28.9)	13.0 (8.0 to 23.0)	10.0 (6.0 to 13.0)
Physical Function: End of therapy	27.8 (22.8 to 40.6)	—	—
Physical Function: Follow-up	27.8 (21.3 to 33.3)	16.0 (9.0 to 28.5)	9.0 (7.0 to 12.0)
Anxiety: Baseline	57.4 (50.8 to 70.0)	9.0 (6.0 to 19.0)	13.0 (8.0 to 23.0)
Anxiety; End of therapy	44.7 (34.4 to 57.4)	—	—
Anxiety: Follow-up	55.8 (39.2 to 62.1)	8.0 (6.5 to 12.5)	16.0 (9.0 to 28.5)
Fatigue: Baseline	71.6 (58.8 to 80.7)	20.0 (17.0 to 30.0)	30.0 (28.0 to 32.0)
Fatigue: End of therapy	65 (32.8 to 73.5)	—	—
Fatigue: Follow-up	68.2 (57.3 to 80.7)	17.0 (9.0 to 25.0)	9.0 (7.0 to 12.0)
Pain Interference: Baseline	67.2 (59.3 to 72.5)	22.0 (16.0 to 24.0)	13.0 (8.0 to 22.0)
Pain Interference: End of therapy	61.8 (51.9 to 67.2)	—	—
Pain Interference: Follow-up	64.4 (55.7 to 76.0)	21.0 (8.5 to 25.5)	16.0 (9.0 to 29.0)

SecondaryFunctional 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.

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.
Reported as:: Median · score on a scale

Functional Disability Inventory- Disability in Children
score on a scale	Chronic Therapy: Arm 1	Acute Therapy: Active	Acute Therapy: Sham
Functional Disability: Baseline	47.5 (41 to 53)	45.5 (25.5 to 49)	44 (39 to 47)
Functional disability: end of therapy	38 (16 to 51)	—	—
Functional Disability: Follow-up	45.5 (27 to 52)	34 (33 to 35)	0 (0 to 0)

SecondaryDisability 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.

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.

No measurements were reported for this outcome.

SecondarySymptom Response Scale

Global symptom improvement scale, score ranging from -7 to +7 (0=no change, positive score indicates improvement while negative score indicates worsening).

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.
Reported as:: Median · positive score on Symptom Response Scale

Symptom Response Scale
positive score on Symptom Response Scale	Chronic Therapy: Arm 1	Acute Therapy: Active	Acute Therapy; Sham
Symptom Response Scale	5 (3 to 6)	5 (4 to 7)	0 (0 to 0)

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Acute Active Percutaneous Neurostimulation	0/10 (0%)	0/10 (0%)	0/10 (0%)
Acute Sham Percutaneous Neurostimulation	0/10 (0%)	0/10 (0%)	0/10 (0%)
Chronic Percutaneous Neurostimulation	0/30 (0%)	0/30 (0%)	7/30 (23.3%)

Most frequent other events

Most frequent other events
Event	Acute Active Percutaneous Neurostimulation	Acute Sham Percutaneous Neurostimulation	Chronic Percutaneous Neurostimulation
Skin irritationSkin and subcutaneous tissue disorders	0/10	0/10	5/30
DiscomfortGeneral disorders	0/10	0/10	1/30
BleedingBlood and lymphatic system disorders	0/10	0/10	1/30

Baseline characteristics

Acute therapy; 15 subjects enrolled; 4 dropped out and 1 ineligible for total of n=10 completed trial Chronic therapy: 32 subjects enrolled; 1 dropped out and 1 ineligible for total of n=30 completed trial

Age, Categorical
Age, Categorical(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
<=18 years	5	5	30	40
Between 18 and 65 years	0	0	0	0
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(years)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
Median	12 (9.0 to 15.0)	13 (10.0 to 15.0)	10.5 (8.5 to 15.5)	11.3 (8.8 to 15.3)

Sex: Female, Male
Sex: Female, Male(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
Female	3	2	18	23
Male	2	3	12	17

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
Hispanic or Latino	0	0	1	1
Not Hispanic or Latino	5	5	29	39
Unknown or Not Reported	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	1	0	0	1
White	4	5	29	38
More than one race	0	0	1	1
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
United States	5	5	30	40

Frequency of emesis episodes
Frequency of emesis episodes(Participants)	Acute Therapy: Active Neurostimulation	Acute Therapy: Sham Neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation	Total
Count of participants	2	4	19	25

Study locations

1 site

Children's Hospital of Wisconsin
Milwaukee, Wisconsin 53226, United States

References and documents

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 28826627 ↗
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 28526575 ↗
Miranda 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 28301217 ↗
Roberts 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 27843360 ↗
Karrento 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 documents

Protocol and statistical analysis plan · Feb 7, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT03434652
Lead sponsor: Medical College of Wisconsin
Responsible party: Katja Karrento (Assistant Professor of Pediatrics, Medical College of Wisconsin) — Principal investigator
First posted: Feb 15, 2018
Start date: Jan 31, 2018
Primary completion: Mar 3, 2021
Completion: Mar 3, 2021
Results posted: Feb 13, 2026
Last update: Feb 13, 2026

Study contacts

Katja Kovacic, MD

principal investigator · Medical College of Wisconsin

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes

View the source record on ClinicalTrials.gov ↗

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