Study Assessing Risk Factors for Abdominal Pain in Children With Inflammatory Bowel Disease

A Pilot Study Assessing Risk Factors for Abdominal Pain in Children With Inflammatory Bowel Disease: The ALLAY Study

To characterize persistent abdominal pain in children with inflammatory bowel disease (IBD) by examining factors such as disease type, activity and location, psychosocial factors, and genetics.

The investigators hypothesize that by using patient pain and psychological assessments in addition to analysis of blood, stool and colonic biopsies, we can better characterize factors that predispose children and adolescents with IBD to have persistent and/or disproportionate abdominal pain.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease
• Intervention / Treatment: Genetic: Genomic DNA; Genetic: RNA analysis; Genetic: Microbiome; Other: Calprotectin; Other: Pain questionnaires; Other: Anxiety/Depression Questionnaires

Detailed Description

This is a prospective longitudinal inception cohort pilot study. The study will hopefully provide information about why there is persistent abdominal pain in children with IBD by examining factors such as disease type, activity and location, psychosocial factors, and genetics. Fifty newly diagnosed pediatric IBD patients, age 8-17 years will be enrolled into the study. There will be 2 control groups as well: pain control population: 20 patients with irritable bowel syndrome (IBS) or functional abdominal pain (FAP) diagnosis who have no evidence of bowel inflammation will serve as a pain control population for patients with no active inflammation. To serve as a control population for patients with no abdominal pain or inflammation, the investigators will include 10 patients with no gastrointestinal symptoms, who undergo colonoscopy for various reasons such as painless rectal bleeding, polyp surveillance, etc. The investigators anticipate completing enrollment in 12 months and allowed another 12 months for follow-up.

The study participants will be seen every 3 months for a year and they will have the following procedures/test performed:

1. Standard of care blood and stool samples
2. Pediatric Ulcerative Colitis Activity Index (PUCAI) or Pediatric Crohn's Disease Activity Index (PCDAI)

They will have an endoscopy performed at diagnosis then at 12 months from enrollment.

A magnetic resonance enterography (MRE) will be done at diagnosis.

The following pain and anxiety tests will be performed throughout the study:

Pain:

Pain Severity Duration Scale (PSDS) Pediatric Catastrophizing Scale-Child/Parents (PCS-C/P) Pain Burden Interview (PBI) Adolescent Pediatric Pain Tool (APPT)

Anxiety:

Revised Children's Anxiety and Depression Scale (RCADS-25) Children's Somatization Index (CSI-24) Adult Responses to Children's Symptoms (ARCS)

Blood, rectal biopsies and stool specimens will be obtained throughout various time points of the study to look at hematology, sed rates, C-reactive protein, genomic DNA, colon RNA, stool microbiome and stool calprotectin.

In summary, the investigators will be examining:

1. Relationship between clinical factors and persistent abdominal pain in patients with IBD

   1. Disease type
   2. Location of disease at diagnosis
   3. Extent of disease at diagnosis
   4. Markers of inflammation at diagnosis and over the course of follow up
   5. Active disease vs. inactive disease over the course of follow up

2. Relationship between psychosocial factors persistent abdominal pain, and remission status, specifically in patients with:

   1. Inactive IBD vs. active IBD
   2. Inactive IBD vs. IBS/FAP
   3. We will compare the parental report to patient report in the above mentioned groups

3. Relationship between gene expression, microbiome, persistent abdominal pain, and remission status, specifically in patients with:

   1. Inactive IBD vs. active IBD
   2. Inactive IBD vs. IBS/FAP
   3. Inactive IBD vs. controls with no abdominal pain

• Study Type: Observational
• Enrollment (Actual): 126

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • CT Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study participants will be recruited from the GI clinic here at Connecticut Children's Medical Center

Description

Inclusion Criteria:

• Age ≥ 8 years or < 18 years (achieved 8th birthday but not yet their 18th birthday)
• IBD established by standard criteria
• Anticipated availability for follow up for ≥ 1 year
• Informed consent/assent

Exclusion Criteria:

• Prior abdominal surgery unrelated to IBD
• Active gastrointestinal infection at time of diagnosis (e.g., C. difficile)
• Other co-morbidities that contribute to abdominal pain (e.g., Familial Mediterranean Fever, metabolic disease)
• Preexisting chronic pain disorder (e.g., fibromyalgia)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
IBD w/abdominal pain; Patients with IBD with abdominal pain. Extra colonic biopsies for RNA analysis. If blood and stool samples are collected for standard of care:blood analyzed for both genomic DNA and calprotectin, and stool analyzed for microbiome. If no blood is drawn then a buccal swab done for the genomic DNA analysis and stool analyzed for calprotectin. Pain questionnaires: Pain Frequency-Severity-Duration Scale Pain Catastrophizing Scale-Child Version Pain Burden Interview Pediatric Quality of Life Inventory Adolescent Pediatric Pain Tool Anxiety/Depression Questionnaires Revised Children's Anxiety and Depression Scale Children's Somatization Inventory Adult Responses to Children's Symptoms	Genetic: Genomic DNA; blood draw; Genetic: RNA analysis; Mucosal Biopsy via colonoscopy; Genetic: Microbiome; Stool microbiome; Other: Calprotectin; stool or blood analysis for calprotectin; Other: Pain questionnaires; PSDS PCS-C/P PBI APPT; Other: Anxiety/Depression Questionnaires; RCADS-25 CSI-24 ARCS
IBD w/out abdominal pain; Patients with IBD and no abdominal pain. Colonoscopy done for standard of care, extra colonic biopsies for RNA analysis. If blood and stool samples are collected for standard of care:blood analyzed for genomic DNA and calprotectin and stool analyzed for microbiome. If no blood is drawn then a buccal swab for the genomic DNA analysis and stool analyzed for calprotectin. Pain questionnaires: Pain Frequency-Severity-Duration Scale Pain Catastrophizing Scale-Child Version Pain Burden Interview Pediatric Quality of Life Inventory Adolescent Pediatric Pain Tool Anxiety/Depression Questionnaires Revised Children's Anxiety and Depression Scale Children's Somatization Inventory Adult Responses to Children's Symptoms	Genetic: Genomic DNA; blood draw; Genetic: RNA analysis; Mucosal Biopsy via colonoscopy; Genetic: Microbiome; Stool microbiome; Other: Calprotectin; stool or blood analysis for calprotectin; Other: Pain questionnaires; PSDS PCS-C/P PBI APPT; Other: Anxiety/Depression Questionnaires; RCADS-25 CSI-24 ARCS
Colonoscopy other reasons no abd pain; Patients who have a colonoscopy for other reasons, rectal bleeding or polyp surveillance, no abdominal pain. Extra colonic biopsies for RNA analysis. If blood and stool samples are collected for standard of care:blood analyzed for genomic DNA and calprotectin and stool analyzed for microbiome. If no blood is drawn then a buccal swab for the genomic DNA analysis and stool analyzed for calprotectin.	Genetic: Genomic DNA; blood draw; Genetic: RNA analysis; Mucosal Biopsy via colonoscopy; Genetic: Microbiome; Stool microbiome; Other: Calprotectin; stool or blood analysis for calprotectin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in abdominal pain from baseline at 3, 6, 9, and 12 months will be assessed using questionnaires	Changes in abdominal pain from baseline then assessed again at 3, 6, 9, and 12 months.	Assessed at baseline then at months 3, 6, 9, and 12

Collaborators and Investigators

• Sponsor: Connecticut Children's Medical Center
• Investigators: Principal Investigator: Victoria Grossi, DO, Connecticut Children's Medical Center

Publications and helpful links

General Publications

• Grossi V, Hyams JS, Glidden NC, Knight BE, Young EE. Characterizing Clinical Features and Creating a Gene Expression Profile Associated With Pain Burden in Children With Inflammatory Bowel Disease. Inflamm Bowel Dis. 2020 Jul 17;26(8):1283-1290. doi: 10.1093/ibd/izz240.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: December 2, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: February 7, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Abdominal Pain; Intestinal Diseases
• Other Study ID Numbers: The ALLAY Study

Plan for Individual participant data (IPD)

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