Neuromodulation for Children With Cystic Fibrosis Experiencing Chronic Abdominal Pain

Neuromodulation With Percutaneous Electrical Nerve Field Stimulation for Children With Cystic Fibrosis Experiencing Chronic Abdominal Pain

Chronic abdominal pain is extremely common in individuals with Cystic Fibrosis (CF). Therapy for chronic abdominal pain is very limited and generally consists of osmotic laxatives or drugs that are used to treat irritable bowel syndrome (IBS), most of which are off-label and not proven to be effective for CF patients. Abdominal pain negatively impacts the quality of life (QOL). With the development of novel therapies for CF, life expectancy has significantly increased. There is, therefore, a critical need to identify treatment pathways for chronic abdominal pain in children with CF.

In humans, abdominal pain is modulated by the vagus nerve. Stimulation of the vagus nerve has been suggested to reduce visceral sensitivity and abdominal pain. IB-stim is the Percutaneous Electrical Nerve Field Stimulation (PENS) device. It is a non-invasive, outpatient therapy. PENFS has been shown to be efficacious in pediatric patients with abdominal pain. The FDA has cleared and classified this device as class II, suggesting minimal to moderate risk.

There is increasing evidence of intestinal inflammation in patients with CF, which could help explain the GI symptoms and differentiate from IBS. Studies have reported increased inflammation in the intestines using fecal calprotectin.

With the implementation of this study, investigators hypothesize that the IB -Stim device will reduce their overall GI inflammation and abdominal pain.

Study Overview

• Status: Terminated
• Conditions: Chronic Pain; Irritable Bowel Syndrome; Cystic Fibrosis
• Intervention / Treatment: Device: Use of neurostimulation device

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• English-speaking and willing to consent and follow the study protocol
• Children with CF aged 11-17 years at the time of enrollment. All races, ethnic groups and both sexes will be included. Patient turning 18 years after enrollment in the study will continue in study and complete remaining study visits.
• Minimum of 2 days of abdominal pain/week for a duration of two months or greater prior to starting the study
• Average weekly abdominal pain score of at least 3 for the previous 2 weeks prior to entering the study (on a 0-10-point rating scale).
• Abdominal pain is not explained by any major organic etiology and comprehensive work up failed to identify any single cause for patients' symptoms

EXCLUSION CRITERIA:

• Patients age of 18 years and over, or less than 11 years at the time of enrollment
• Patients who cannot provide informed consent or do not speak English
• Patients with abdominal pain that can be explained clinically by other GI diagnoses other than CF per study doctor's judgement
• History of cranial nerve or major abdominal surgeries in last 6 months
• Patients with underlying neurologic conditions, including history of ongoing seizures or traumatic brain injury within last 6 months
• Patients with dermatologic conditions affecting the ears (i.e. psoriasis), or with cuts or abrasions to the external ear that would interfere with electrode placement
• Patients with hemophilia or other bleeding disorders
• Patients with any implanted electromagnetic device
• Inability to comply with study protocol and follow up, per study doctor's judgement.
• Pregnant females, females who are breastfeeding or who believe they may wish to become pregnant during the course of the study
• Males and females of reproductive potential who are unwilling to use effective measures (chosen in consultation with their health care provider) to avoid becoming pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Patient open label intervention arm

Device: Use of neurostimulation device; In humans, abdominal pain is modulated by the vagus nerve. Stimulation of the vagus nerve has been suggested to reduce visceral sensitivity and abdominal pain. IB-stim is the Percutaneous Electrical Nerve Field Stimulation (PENS) device. It is a non-invasive, outpatient therapy. PENFS has been shown to be efficacious in pediatric patients with abdominal pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IBS Severity Scoring System-Change Between Baseline and Week 8 is Reported.	IBS-SSS is a tool for assessing IBS. Please refer to the following for further understanding of this tool. It records Part 1- Severity Score( 0-500 where 0 is no symptom and 500 is the severe symptoms) and Part 2 ' Other IBS Data' under which includes bowel habits, consistency of bowel movements, red flag symptoms, site of pain and absence from work due to IBS. We cannot use part 2 because it does not have assigned scoring system and as such not suitable for patients with CF due to know genetic mutation in CF causing many similar symptoms of IBS. It has nine stem q: five questions ( in Part 1) have scores of between 0 and 100 for each question, based on visual analogue scales, each minimum of 0 to max of 100.We report combined sub score at baseline and week 8. A score below 75 is seen in healthy people or in remission of IBS, 75-175 indicates mild disease, 175-300 moderate disease and over 300 severe. The score is interpreted as an absolute change from the baseline and at week 8.	baseline and 8 weeks
CFQ-R and PedsQL Gastrointestinal Scale Score in Response to IB-Stim Treatment- Baseline and Week 8 Reported	Name of categories/domains CFQ-R: 9 Quality of life domains: Physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions. 3 symptom scales: Weight, respiratory, and digestion. Scaling of items: 5 distinct 4-point Likert scales (e.g., always/often/ sometime/never) Scoring: Range from 0 to 100, with higher scores indicating better health. PedsQL consists of 74 items comprising 14 dimensions Likert scale from 0 to 4.Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0.Total Score: Sum of all the items over the number of items answered on all the Scales. PedsQL scoring interpretation: In general, the higher scores indicating better health for this measure. Baseline and week 8 reported	baseline and 8 weeks
Reduction in Stool Calprotectin Inflammatory Markers in Response to IB-Stim-change Between Two Time Point is Reported.	Investigators hypothesize that at 4 weeks following PENFS treatment initiation, there will be a reduction in stool calprotectin to baseline. The higher the value, worse the disease. The value above 200 ug/mg is considered to be suggestive of significant inflammation in the gut.	Baseline and week 4

Collaborators and Investigators

• Sponsor: St. Louis University
• Collaborators: Washington University School of Medicine

Publications and helpful links

General Publications

• Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: August 23, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Pancreatic Diseases; Fibrosis; Irritable Bowel Syndrome; Chronic Pain; Abdominal Pain; Cystic Fibrosis
• Other Study ID Numbers: 31972

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Unsure about the number of participants and their willingness to allow us to share the data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No