Functional Gastrointestinal Disorders
Conditions
Brief 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 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: 1. To define adolescent functional nausea into subtypes based on clinical characterization and physiologic testing. 2. 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. 3. Investigate possible brain functional connectivity changes induced by auricular neurostimulation compared to patients with irritable bowel syndrome and healthy controls
Interventions
DEVICEActive Auricular Neurostimulation
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.
DEVICESham Auricular Neurostimulation
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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All participants, investigators and study team members blinded
Intervention model description
Randomized, double blind placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
11 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nausea Severity Scale | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nausea Profile | After 4 weeks of therapy | 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. |
| Baxter Retching Faces Scale | Average score during week 4 of therapy | 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. |
Countries
United States
Participant flow
Pre-assignment details
n=1 participant excluded after enrollment but prior to randomization due to ineligibility (alternate diagnosis discovered)
Participants by arm
| Arm | Count |
|---|---|
| Auricular Neurostimulation Intervention: Active Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks
Active Auricular Neurostimulation: 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. | 50 |
| Sham Auricular Neurostimulation Intervention: Sham (Inactive) Percutaneous Electrical Nerve Field Stimulation (PENFS) 5 days/week x 4 weeks.
Sham Auricular Neurostimulation: 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. | 46 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Auricular Neurostimulation | Sham Auricular Neurostimulation | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 48 Participants | 46 Participants | 94 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Continuous | 15.04 years | 15.79 years | 15.13 years |
| Baxter Retching faces scale | 2.83 units on a scale | 3.14 units on a scale | 2.99 units on a scale |
| Nausea Profile | 44.44 units on a scale | 49.67 units on a scale | 47.08 units on a scale |
| Nausea Severity Scale | 2.85 units on a scale | 2.75 units on a scale | 2.78 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 48 Participants | 45 Participants | 93 Participants |
| Region of Enrollment United States | 50 participants | 46 participants | 96 participants |
| Sex: Female, Male Female | 39 Participants | 38 Participants | 77 Participants |
| Sex: Female, Male Male | 11 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 46 |
| other Total, other adverse events | 11 / 50 | 16 / 46 |
| serious Total, serious adverse events | 0 / 50 | 0 / 46 |
Outcome results
Primary
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.
Time frame: After 4 weeks of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Auricular Neurostimulation | Nausea Severity Scale | 2.18 units on a scale |
| Sham Auricular Neurostimulation | Nausea Severity Scale | 2.45 units on a scale |
Secondary
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.
Time frame: Average score during week 4 of therapy
Population: Some missing data as not all participants completed the daily diaries
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Auricular Neurostimulation | Baxter Retching Faces Scale | 2.29 units on a scale |
| Sham Auricular Neurostimulation | Baxter Retching Faces Scale | 3.43 units on a scale |
Secondary
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.
Time frame: After 4 weeks of therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Auricular Neurostimulation | Nausea Profile | 33.33 units on a scale |
| Sham Auricular Neurostimulation | Nausea Profile | 28.43 units on a scale |