Trial Outcomes & Findings for Efficacy of Ear Neurostimulation for Adolescents With Functional Abdominal Pain (NCT NCT02367729)

NCT ID: NCT02367729

Last Updated: 2018-11-08

Results Overview

One-page, 6-item pain measure assessing pain symptoms over the past week. Measures the typical and worst pain intensity, frequency and duration over the past week in units on a scale from 0 to 10 (10 being the worst pain imaginable). Worst pain = primary outcome.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

115 participants

Primary outcome timeframe

Change from Baseline to Week 4

Results posted on

2018-11-08

Participant Flow

Eligible subjects ages 11-18 years, recruited from the outpatient Gastroenterology clinic at the Children's Hospital of Wisconsin between September 2015 and November 2016.

Subjects were excluded if there were any changes to their current medications or any new medications added during the two weeks prior to study start. Any subject with a new diagnosis of an organic medical condition was also excluded.

Participant milestones

Participant milestones
Measure
Neurostimulator
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device (without electrical charge), worn for 5 days each week x 4 weeks.
Overall Study
STARTED
60
55
Overall Study
COMPLETED
57
47
Overall Study
NOT COMPLETED
3
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Neurostimulator
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device (without electrical charge), worn for 5 days each week x 4 weeks.
Overall Study
Organic disorder diagnosed
2
1
Overall Study
Adverse Event
1
2
Overall Study
Withdrawal by Subject
0
5

Baseline Characteristics

Efficacy of Ear Neurostimulation for Adolescents With Functional Abdominal Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Neurostimulator
n=57 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=47 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Total
n=104 Participants
Total of all reporting groups
Age, Continuous
15.3 years
n=5 Participants
15.6 years
n=7 Participants
15.3 years
n=5 Participants
Sex: Female, Male
Female
51 Participants
n=5 Participants
43 Participants
n=7 Participants
94 Participants
n=5 Participants
Sex: Female, Male
Male
6 Participants
n=5 Participants
4 Participants
n=7 Participants
10 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · White
49 Participants
n=5 Participants
44 Participants
n=7 Participants
93 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · African American
6 Participants
n=5 Participants
2 Participants
n=7 Participants
8 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Hispanic
1 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Asian
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Region of Enrollment
United States
57 Participants
n=5 Participants
47 Participants
n=7 Participants
104 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Change from Baseline to Week 4

Population: Modified intent to treat population (all subjects who received minimum one week of therapy and with at least two available data points). Last observation carried forward (LOCF) imputation method.

One-page, 6-item pain measure assessing pain symptoms over the past week. Measures the typical and worst pain intensity, frequency and duration over the past week in units on a scale from 0 to 10 (10 being the worst pain imaginable). Worst pain = primary outcome.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=57 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=47 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Pain Frequency-Severity-Duration Scale (PFSD) Score
5.0 units on a scale
Interval 4.0 to 7.0
7.0 units on a scale
Interval 5.0 to 9.0

SECONDARY outcome

Timeframe: Change from Baseline to week 4 in Nausea Profile score.

Population: Modified intent to treat population (all subjects who received minimum one week of therapy and with at least two available data points). Last observation carried forward (LOCF) imputation method.

Two page, 17-item questionnaire which measures the subjective experience of nausea on a scale from 0 (not at all) to 9 (severely) across three dimensions: 1) somatic distress; 2) gastrointestinal distress and 3) emotional distress. Total score 153.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=57 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=47 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Nausea Profile
25.5 units on a scale
Interval 11.8 to 43.0
20.0 units on a scale
Interval 8.0 to 31.5

SECONDARY outcome

Timeframe: Change from Baseline (Pre) to 2-3 months after end of therapy (Post)

Population: Modified intent to treat population (all subjects who received minimum one week of therapy and with at least two available data points). Last observation carried forward (LOCF) imputation method.

State-Trait Anxiety Inventory for Children (STAI-C). State anxiety measured by 20-item questionnaire assessing anxiety at a particular moment in time on a 3-point rating scale. Raw scores (range 20-60) were converted to normalized T-Scores based on a population of healthy school children (mean=50; standard deviation=10) with higher score indicating worse outcome. Effects of intervention on state anxiety was assessed before (pre) and after (post) therapy.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=49 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=42 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
State-Trait Anxiety Inventory for Children (STAI-C)
State Anxiety Pre
54.0 T-score
Interval 49.0 to 60.5
54.0 T-score
Interval 46.0 to 56.0
State-Trait Anxiety Inventory for Children (STAI-C)
State Anxiety Post
52.0 T-score
Interval 46.0 to 58.5
54.0 T-score
Interval 49.0 to 58.0

SECONDARY outcome

Timeframe: Change from Baseline (Pre) to 2-3 months after end of therapy (Post)

Population: Modified intent to treat population (all subjects who received minimum one week of therapy and with at least two available data points). Last observation carried forward (LOCF) imputation method.

A 7-item instrument that measures quality of life in relation to health. Each question has five response options (scored 1-5 units on a scale). A total raw sum score is generated, ranging from lowest score of 7 and highest score of 35 with higher scores indicating better outcome (improved quality of life). The raw score is converted to a standardized T-score (mean=50; standard deviation=10) based on a population of healthy children. T-scores were compared before (Pre) and after (Post) treatment intervention.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=50 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=43 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health (PGH-7)
PROMIS Pre
42.1 T-score
Interval 35.6 to 45.7
37.2 T-score
Interval 34.0 to 43.9
Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health (PGH-7)
PROMIS Post
42.1 T-score
Interval 36.4 to 46.6
38.8 T-score
Interval 34.0 to 42.1

SECONDARY outcome

Timeframe: Change from Baseline (Pre) to 2-3 months after end of therapy (Post)

Population: Modified intent to treat population (all subjects who received minimum one week of therapy and with at least two available data points). Last observation carried forward (LOCF) imputation method.

15-item instrument, each question rated on a five-point scale (0="no trouble" to 4="impossible"), indicating how much difficulty subjects have doing common childhood activities because of their physical health. A total score is summed (range 0-60) with higher score indicating worse outcome (greater pain-related disability). Scored were compared before (Pre) and after (Post) treatment intervention.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=50 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=43 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Functional Disability Inventory (FDI)
FDI Pre
17.0 units on a scale
Interval 7.8 to 27.5
17.0 units on a scale
Interval 11.0 to 29.0
Functional Disability Inventory (FDI)
FDI Post
11 units on a scale
Interval 6.0 to 22.3
17.0 units on a scale
Interval 6.0 to 26.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline only (diagnostic criteria)

Nine-page, validated, parent-report questionnaire that assesses symptoms associated with pediatric functional GI disorders to diagnose the following specific Rome III criteria: Irritable Bowel Syndrome, Functional Dyspepsia, Abdominal Migraine, Functional Abdominal Pain and Functional Abdominal Pain Syndrome. The number of participants with these specific diagnoses at baseline were reported, including overlapping diagnoses.

Outcome measures

Outcome measures
Measure
Neurostimulator
n=57 Participants
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=47 Participants
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III (QPGS-RIII), Reporting the Number of Participants With Specific Diagnoses
Functional Dyspepsia
12 Participants
11 Participants
Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III (QPGS-RIII), Reporting the Number of Participants With Specific Diagnoses
Functional Abdominal Pain
1 Participants
0 Participants
Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III (QPGS-RIII), Reporting the Number of Participants With Specific Diagnoses
Irritable Bowel Syndrome
28 Participants
23 Participants
Questionnaire on Pediatric Gastrointestinal Symptoms, Rome III (QPGS-RIII), Reporting the Number of Participants With Specific Diagnoses
Abdominal Migraine
16 Participants
13 Participants

Adverse Events

Neurostimulator

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Sham Neurostimulator

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Neurostimulator
n=57 participants at risk
Auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Neurostimulator: Non-invasive, battery operated neurostimulator of the external ear worn for 5 days each week x 4 weeks.
Sham Neurostimulator
n=47 participants at risk
Inactive auricular neurostimulator treatment x 5 days each week for 4 consecutive weeks Sham: Inactive neurostimulator device pre-programmed to be inactive. To be worn for 5 days each week x 4 weeks.
General disorders
Ear discomfort
5.3%
3/57 • Number of events 3 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.
6.4%
3/47 • Number of events 3 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.
Immune system disorders
Adhesive allergy
1.8%
1/57 • Number of events 1 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.
4.3%
2/47 • Number of events 2 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.
Nervous system disorders
Syncope
0.00%
0/57 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.
2.1%
1/47 • Number of events 1 • 1.5 years (during time of subject participation and through follow-up period)
Information on any adverse events were systematically collected by the research staff at each visit prior to placement of a new neurostimulator and at the follow-up visit.

Additional Information

Dr. Katja Kovacic

Medical College of Wisconsin

Phone: 4142663915

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place