Trial Outcomes & Findings for Auricular Neurostimulation for Cyclic Vomiting Syndrome (NCT NCT03434652)

Last Updated: 2026-02-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

47 participants

Primary outcome timeframe

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.

Results posted on

2026-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	Acute Therapy: Cross-over Active Neurostimulation Subject randomized to 5 days of active vs sham neurostimulation therapy during the first illness cycle. With second illness cycle, each subject will cross over to the other arm for 5 days of active vs. sham neurostimulation therapy. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy: Cross-over Sham Neurostimulation Subject randomized to 5 days of active vs sham neurostimulation therapy during the first illness cycle. With second illness cycle, each subject will cross over to the other arm for 5 days of active vs. sham neurostimulation therapy. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy: Active (Open-label) Neurostimulation Each participant receives active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Overall Study STARTED	8	7	32
Overall Study COMPLETED	5	5	30
Overall Study NOT COMPLETED	3	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Acute Therapy: Cross-over Active Neurostimulation Subject randomized to 5 days of active vs sham neurostimulation therapy during the first illness cycle. With second illness cycle, each subject will cross over to the other arm for 5 days of active vs. sham neurostimulation therapy. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy: Cross-over Sham Neurostimulation Subject randomized to 5 days of active vs sham neurostimulation therapy during the first illness cycle. With second illness cycle, each subject will cross over to the other arm for 5 days of active vs. sham neurostimulation therapy. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy: Active (Open-label) Neurostimulation Each participant receives active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Overall Study Lost to Follow-up	2	2	1
Overall Study Physician Decision	1	0	1

Baseline Characteristics

Auricular Neurostimulation for Cyclic Vomiting Syndrome

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Population: Study design for Acute treatment arm was subsequently deemed unfeasible and the trial terminated early for the Acute treatment arm.

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=5 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=5 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm n=30 Participants Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Rhodes Index of Nausea, Vomiting & Retching (INVR) Baseline INVR	3.25 score on a scale Standard Deviation 3.95	5.80 score on a scale Standard Deviation 9.17	10.43 score on a scale Standard Deviation 9.78
Rhodes Index of Nausea, Vomiting & Retching (INVR) End of therapy INVR	0.75 score on a scale Standard Deviation 1.50	1.50 score on a scale Standard Deviation 3.00	2.31 score on a scale Standard Deviation 3.88

SECONDARY outcome

Timeframe: 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.

Population: This outcome (daily pain severity) was designed for the Acute Therapy Arm only as it assesses daily pain during an acute intervention. The chronic therapy arm did not include this outcome measure due to the longer term treatment and therefore, there is no data for the chronic therapy arm.

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).

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=2 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=3 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Numeric Pain Scale Baseline	4 score on a scale Standard Deviation 0	4.7 score on a scale Standard Deviation 3.4	—
Numeric Pain Scale End of therapy	1 score on a scale Standard Deviation 1	1.3 score on a scale Standard Deviation 1.2	—

SECONDARY outcome

Timeframe: 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).

Population: Complete data captured on 26 participants in Chronic Therapy arm. No data captured on Acute Therapy Arm for this outcome measure as this arm deemed unfeasible due to subjects being too ill to return for on site visits and subsequently dropped out of study. Contrary to the daily surveys completed in home setting (outcome measure 2), data was not obtained for the on site visits at the end of therapy.

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).

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=26 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=5 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm n=5 Participants Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Anxiety Baseline	63.5 score on STAI state anxiety scale Interval 52.0 to 70.0	28 score on STAI state anxiety scale Interval 25.0 to 36.0	29 score on STAI state anxiety scale Interval 26.0 to 34.5
Anxiety End of therapy	51 score on STAI state anxiety scale Interval 44.0 to 54.0	—	—
Anxiety Follow-up	49 score on STAI state anxiety scale Interval 44.0 to 54.0	23.5 score on STAI state anxiety scale Interval 22.5 to 26.5	36 score on STAI state anxiety scale Interval 30.0 to 42.0

SECONDARY outcome

Timeframe: 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.

Population: Complete data capture on 27 participants (Chronic Therapy Arm). No data captured on Acute Therapy Arm for this outcome measure as this arm deemed unfeasible due to subjects being too ill to return for on site visits and subsequently dropped out of study. Contrary to the daily surveys completed in home setting (outcome measure 2), data was not obtained for the on site visits at the end of therapy.

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.

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=27 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=5 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm n=5 Participants Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Physical Function: Baseline	25.4 score on a scale Interval 22.8 to 28.9	13.0 score on a scale Interval 8.0 to 23.0	10.0 score on a scale Interval 6.0 to 13.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Physical Function: End of therapy	27.8 score on a scale Interval 22.8 to 40.6	—	—
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Physical Function: Follow-up	27.8 score on a scale Interval 21.3 to 33.3	16.0 score on a scale Interval 9.0 to 28.5	9.0 score on a scale Interval 7.0 to 12.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Anxiety: Baseline	57.4 score on a scale Interval 50.8 to 70.0	9.0 score on a scale Interval 6.0 to 19.0	13.0 score on a scale Interval 8.0 to 23.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Anxiety; End of therapy	44.7 score on a scale Interval 34.4 to 57.4	—	—
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Anxiety: Follow-up	55.8 score on a scale Interval 39.2 to 62.1	8.0 score on a scale Interval 6.5 to 12.5	16.0 score on a scale Interval 9.0 to 28.5
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Fatigue: Baseline	71.6 score on a scale Interval 58.8 to 80.7	20.0 score on a scale Interval 17.0 to 30.0	30.0 score on a scale Interval 28.0 to 32.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Fatigue: End of therapy	65 score on a scale Interval 32.8 to 73.5	—	—
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Fatigue: Follow-up	68.2 score on a scale Interval 57.3 to 80.7	17.0 score on a scale Interval 9.0 to 25.0	9.0 score on a scale Interval 7.0 to 12.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Pain Interference: Baseline	67.2 score on a scale Interval 59.3 to 72.5	22.0 score on a scale Interval 16.0 to 24.0	13.0 score on a scale Interval 8.0 to 22.0
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Pain Interference: End of therapy	61.8 score on a scale Interval 51.9 to 67.2	—	—
Patient Reported Outcomes Measurement Information Systems- Health-Related Quality of Life Pain Interference: Follow-up	64.4 score on a scale Interval 55.7 to 76.0	21.0 score on a scale Interval 8.5 to 25.5	16.0 score on a scale Interval 9.0 to 29.0

SECONDARY outcome

Timeframe: 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.

Population: Complete data captured on 30 participants in Chronic Therapy arm. No data captured on Acute Therapy Arm for this outcome measure as this arm deemed unfeasible due to subjects being too ill to return for on site visits and subsequently dropped out of study. Contrary to the daily surveys completed in home setting (outcome measure 2), data was not obtained for the on site visits at the end of therapy.

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.

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=30 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=4 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm n=5 Participants Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Functional Disability Inventory- Disability in Children Functional Disability: Baseline	47.5 score on a scale Interval 41.0 to 53.0	45.5 score on a scale Interval 25.5 to 49.0	44 score on a scale Interval 39.0 to 47.0
Functional Disability Inventory- Disability in Children Functional disability: end of therapy	38 score on a scale Interval 16.0 to 51.0	—	—
Functional Disability Inventory- Disability in Children Functional Disability: Follow-up	45.5 score on a scale Interval 27.0 to 52.0	34 score on a scale Interval 33.0 to 35.0	0 score on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Population: No data collected as no adult participants enrolled.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Data captured on 29 participants in Chronic Therapy arm.

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

Outcome measures

Outcome measures
Measure	Acute Therapy Arm: Active Neurostimulation n=29 Participants Subject randomized to active (vs sham) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (sham vs. active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy Arm: Sham Neurostimulation n=5 Participants Subject randomized to sham (vs active) neurostimulation therapy during the first illness cycle for 5 days of therapy. With next illness cycle, each subject will cross over to the other (active vs sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy Arm n=1 Participants Active, open label percutaneous neurostimulation therapy x 6 consecutive weeks
Symptom Response Scale	5 positive score on Symptom Response Scale Interval 3.0 to 6.0	5 positive score on Symptom Response Scale Interval 4.0 to 7.0	0 positive score on Symptom Response Scale Interval 0.0 to 0.0

Adverse Events

Acute Active Percutaneous Neurostimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Acute Sham Percutaneous Neurostimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Chronic Percutaneous Neurostimulation

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Acute Active Percutaneous Neurostimulation n=10 participants at risk Each subject randomized to active vs sham therapy during 1st illness cycle (5 days) after enrollment, then cross over to the other (active vs sham) during the 2nd illness cycle (5 days). Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Sham Percutaneous Neurostimulation n=10 participants at risk Each subject randomized to active vs sham therapy during 1st illness cycle (5 days) after enrollment, then cross over to the other (active vs sham) during the 2nd illness cycle (5 days). Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Percutaneous Neurostimulation n=30 participants at risk Chronic (prophylactic), active therapy (open label) x 6 consecutive weeks of intervention. Percutaneous neurostimulation: Auricular percutaneous neurostimulation
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/10 • 6 months Adverse events assessed at each encounter	0.00% 0/10 • 6 months Adverse events assessed at each encounter	16.7% 5/30 • Number of events 5 • 6 months Adverse events assessed at each encounter
General disorders Discomfort	0.00% 0/10 • 6 months Adverse events assessed at each encounter	0.00% 0/10 • 6 months Adverse events assessed at each encounter	3.3% 1/30 • Number of events 1 • 6 months Adverse events assessed at each encounter
Blood and lymphatic system disorders Bleeding	0.00% 0/10 • 6 months Adverse events assessed at each encounter	0.00% 0/10 • 6 months Adverse events assessed at each encounter	3.3% 1/30 • Number of events 1 • 6 months Adverse events assessed at each encounter

Additional Information

Katherine Siegel, Research Manager, Division of Pediatric Gastroenterology

Medical College of Wisconsin

Phone: 4142663915

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Acute Therapy: Active Neurostimulation n=5 Participants Each subject randomized to receive 5 days of active (vs. sham) neurostimulation therapy during the first illness cycle. With the next illness cycle, each subject will cross over to sham (or active) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Acute Therapy: Sham Neurostimulation n=5 Participants Each subject randomized to receive 5 days of sham (vs active) neurostimulation therapy during the first illness cycle. With the next illness cycle, each subject will cross over to active (or sham) intervention for 5 days. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Chronic Therapy; Active (Open-label) Neurostimulation n=30 Participants Active, open label neurostimulation therapy x 6 consecutive weeks. Percutaneous neurostimulation: Auricular percutaneous neurostimulation	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	5 Participants n=6 Participants	5 Participants n=6 Participants	30 Participants n=12 Participants	40 Participants n=1267 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Age, Categorical >=65 years	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Age, Continuous	12 years n=6 Participants	13 years n=6 Participants	10.5 years n=12 Participants	11.3 years n=1267 Participants
Sex: Female, Male Female	3 Participants n=6 Participants	2 Participants n=6 Participants	18 Participants n=12 Participants	23 Participants n=1267 Participants
Sex: Female, Male Male	2 Participants n=6 Participants	3 Participants n=6 Participants	12 Participants n=12 Participants	17 Participants n=1267 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=12 Participants	1 Participants n=1267 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=6 Participants	5 Participants n=6 Participants	29 Participants n=12 Participants	39 Participants n=1267 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Race (NIH/OMB) Black or African American	1 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	1 Participants n=1267 Participants
Race (NIH/OMB) White	4 Participants n=6 Participants	5 Participants n=6 Participants	29 Participants n=12 Participants	38 Participants n=1267 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=12 Participants	1 Participants n=1267 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=12 Participants	0 Participants n=1267 Participants
Region of Enrollment United States	5 Participants n=6 Participants	5 Participants n=6 Participants	30 Participants n=12 Participants	40 Participants n=1267 Participants
Frequency of emesis episodes	2 Participants n=6 Participants	4 Participants n=6 Participants	19 Participants n=12 Participants	25 Participants n=1267 Participants