Biofeedback in Pediatric Inflammatory Bowel Disease

Impact of a Biofeedback Intervention on Microbiome, Metabolome, and Clinical Outcomes in Pediatric IBD

This prospective, randomized, longitudinal, controlled project will occur in two phases. Phase 1 is the pre-diagnosis data collection for treatment-naïve participants who are referred for a diagnostic endoscopy/colonoscopy due to suspicion of IBD. Phase 2 (RCT) is only for patients who are diagnosed with IBD. These patients will be randomized to receive biofeedback intervention daily for 8 weeks or no biofeedback intervention. All participants will receive physician directed standard of care treatment.

Study Overview

• Status: Withdrawn
• Conditions: IBD
• Intervention / Treatment: Behavioral: Biofeedback

Detailed Description

The inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), affects 3 million Americans. In approximately 25-30% of patients, onset of these chronic diseases occurs prior to the age of 20. Despite medical advances in new therapies, the clinical remission rate on biologics is less than 50% and a significant number of patients will lose response to anti-TNF therapy over time. In addition, patients that require a change in therapy will have a lower response rate to a different biologic. Additional therapies and mechanisms that affect disease activity need to be investigated to identify complimentary treatments that can further impact remission rates without increasing side effects such as lymphoma.

Environmental factors, such as stressor exposure, can exacerbate mucosal inflammation. Patients with IBD report a lower quality of life, as well as increased anxiety and depression. Psychological interventions may improve disease activity. This study will test, using a randomized clinical trial (RCT) design, whether biofeedback intervention will attenuate disease activity. If efficacious, this study will provide a rationale for establishing biofeedback as a complimentary therapy to standard of care to ameliorate stress-induced increases in chronic inflammation.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ross Maltz, MD; Phone Number: 614-722-3450; Email: Ross.Maltz@nationwidechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The inclusion criteria for Phase 1 are:

1. Age 8-17 years
2. Referred for a diagnostic colonoscopy with strong clinical concern for IBD
3. Live within a 2 hour drive of NCH

There is one additional inclusion criterion for Phase 2:

1. Patients have been diagnosed with IBD

Exclusion Criteria:

1. Participants are excluded if they have a comorbid chronic illness, perianal disease, current corticosteroid treatment, taking antibiotics within the last 3 months, psychological disorders that they are undergoing treatment or taking medication for at that time, or undergoing psychological treatments such as cognitive behavioral therapy, mindfulness, or biofeedback therapy at the time of enrollment.
2. Age and language are limited by the demands of the study (questionnaire completion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Participants will not receive biofeedback intervention.
Experimental: Biofeedback; Participants will receive a biofeedback intervention daily for 8 weeks. Each biofeedback session lasts approximately 10 minutes.	Behavioral: Biofeedback; They will also be taught how to use the biofeedback app and Inner Balance device. Additionally, they will also be educated on the principles of biofeedback and its benefits and taught how to maximize HRV by using self-regulation breathing techniques, guided imagery, and/ or self-talk.They will be given an Inner Balance device, which is an ear sensor that connects to an apple device that measures heart rate variability (HRV) and gives them access to an app that is designed to help them improve their HRV. They will be asked to use this device daily for 10 mins for the duration of the 8-week intervention. Patients and the research coordinator will have access to all of their sessions and results. The research coordinator will monitor compliance via the Heartcloud associated with their device and encourage adherence throughout the 8-week biofeedback intervention.; Other Names: Inner Balance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crohn's disease mucosal healing	Simple endoscopic score for CD (SES-CD) scores ileum, right colon, transverse, left colon, and rectum for the degree of ulceration. Scale ranges from 0-3, total score is calculated from sum of all variables for all 5 locations. Scores range from 0-60. Higher scores indicate worse inflammation.	pre-diagnosis to 12 month follow up
Ulcerative Colitis Mucosal healing	Mayo endoscopic scores for the degree of ulceration. Scores range from 0-3. Higher scores indicate worse inflammation.	pre-diagnosis to 12 month follow up
Disease activity( Fecal calprotectin)	Fecal calprotectin levels from stool	pre diagnosis to 12 month follow up
Disease Activity (Crohn's disease)	Pediatric Crohn's Disease Activity Index total score. A standard measure of disease severity that is comprised of information obtained from patient recall (pain severity, stool frequency, limitation of activities), examination (weight, height, abdominal tenderness, perirectal disease, extra- intestinal manifestations), and laboratory data. The Pediatric Crohn's Disease Activity Index total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up. Higher scores indicate more severe disease. Scores range from 0-100.	pre diagnosis to 12 month follow up
Disease Activity ( Ulcerative Colitis)	Pediatric Ulcerative Colitis Activity Index total score. A standard Pediatric Ulcerative Colitis Activity Index. a standard measure of disease severity that is comprised pain severity, stool frequency and consistency, rectal bleeding, nocturnal bowel movements, and limitation of activities. The Pediatric Ulcerative Colitis Activity Index total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up. Higher scores indicate more severe disease. Scores range from 0-85.	pre diagnosis to 12 month follow up
Stress	PROMIS Pediatric Psychological Stress Experiences.Scores range from 0-60, with higher scores indicating higher levels of stress.Total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up.	pre-diagnosis to 12 month follow up
Anxiety	PROMIS Pediatric Anxiety Short Form. Scores range from 0-60, with higher scores indicating higher levels of anxiety. Total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up.	pre-diagnosis to 12 month follow up
Pediatric Quality of life	PedsQL. Scores range from 0-100 with higher scores indicating higher quality of life. Total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up.	pre-diagnosis to 12 month follow up
Depression	Children's Depression Inventory short form. Scores range from 0-54, with higher scores indicating higher levels of depression. Total score will be used from pre-diagnosis, post-intervention, 4 months post-intervention, and 12 month follow up.	pre-diagnosis to 12 month follow up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stress-related changes in the microbiome	Microbiome α and β-diversity will be examined at pre-diagnosis, post-intervention, 4 month post-intervention, and 12 month follow-up to determine possible relationships between overall community structure between participants that received the intervention of biofeedback vs participants that were controls.	pre diagnosis to 12 month follow up
Stress-related changes in the metabolome.	Random Forest (RF) and Boruta feature selection will be used from pre-diagnosis, post-intervention, 4 month post-intervention, and 12 month follow-up to identify metabolites and microbes.To further interpret the biological function of predictive metabolites, pathway enrichment analysis will be performed using the RaMP database, which integrates biological pathway and metabolite annotions from multiple sources (e.g. HMDB, KEGG, REACTOME, WikiPathways).	pre diagnosis to 12 month follow up

Collaborators and Investigators

• Sponsor: Ross Maltz
• Investigators: Principal Investigator: Ross Maltz, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): September 9, 2022
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): February 1, 2025

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 17, 2020

Study Record Updates

• Last Update Posted (Actual): December 23, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: biofeedback; pediatric
• Other Study ID Numbers: IRB18-01100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No