Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease

This research study will evaluate if specific blood, stool and MRI tests can tell the difference between bowel wall inflammation without scarring and bowel wall inflammation with scarring that can cause bowel blockages requiring surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Diagnostic test: blood biomarkers; Diagnostic test: stool biomarkers; Diagnostic test: MRI imaging

Detailed Description

This multi-center study will test the accuracy of individual and combined MRI and blood-based diagnostic tools in both children and adults with small bowel CD. We will determine the accuracy of a composite tool (including its multiple individual biomarkers) for defining the relative amounts of intestinal inflammation versus scarring in patients at the time of surgery (B2 disease) and in patients at an early stage of disease prior to complications (B1 disease).

• Study Type: Observational
• Enrollment (Estimated): 232

Contacts and Locations

• Study Contact: Name: Becky Imbus; Phone Number: 513-636-9403; Email: rebecca.imbus@cchmc.org

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory/Children's Healthcare of Atlanta
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Aim 1 - Children and adults undergoing surgical small bowel resection for structuring CD; Aim 2 - children and adults that have known uncomplicated inflammatory small bowel CD (B1phenotype) AND healthy non-IBD participants

Description

Inclusion Criteria:

• Aim 1 (CD participants)

  1. Aged 8-70 years
  2. Undergoing first surgical distal (ileal) small bowel resection for structuring (B2 phenotype) Crohn's disease as determined by CTE or MRE or ileocolonoscopy
  3. English speaking

• Aim 2 (CD participants)

  1. Age 8 to 70 years
  2. Uncomplicated inflammatory small bowel CD based on clinical CTE or MRE or ileocolonoscopy performed within 6 months prior to enrollment (CD participants only)
  3. English speaking

• Aim 2 (Control participants)

  1. Age 8 to 70 years
  2. English speaking

Exclusion Criteria:

• Aim1 (CD participants)

  1. B1 or B3 (i.e., fistula, abscess, phlegmon/inflammatory mass) CD phenotype
  2. Prior small bowel surgery, including but not limited to surgical resection, stricturoplasty, or endoscopic treatment of a small bowel stricture
  3. Anything to eat or drink within 4 hours of study visit (participants may take their required medications with a little water)
  4. Known pregnancy (Note: Institutional policies/procedures will be followed for pregnancy screening)
  5. Contraindication for MRI (e.g., surgical implant, claustrophobia). Note: To be determined based on local procedures.

• Aim 2 (CD participants)

  1. Stenotic ileocecal valve at colonoscopy
  2. Prior small bowel surgery, including but not limited to surgical resection, stricturoplasty, or endoscopic treatment of a small bowel stricture
  3. Anything to eat or drink within 4 hours of study visit (participants may take their required medications with a little water)
  4. Known pregnancy (Note: Institutional policies/procedures will be followed for pregnancy screening)
  5. Contraindication for MRI (e.g., surgical implant, claustrophobia). Note: To be determined based on local procedures.

• Aim 2 (Control participants)

  1. Any known gastrointestinal tract disease
  2. Any known inflammatory/autoimmune disease involving another organ system (e.g., rheumatoid arthritis, scleroderma, multiple sclerosis).
  3. Fecal calprotectin level of ˃100 mcg.gm will be excluded from further analysis and replaced.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aim 1 Crohn Disease participants (B2 phenotype); Crohn's Disease participants scheduled for ileal small bowel resection; No intervention; observational only; collection of blood, stool, and perform MRI; completion of Crohn's Activity Questionnaire	Diagnostic test: blood biomarkers; biomarkers to distinguish fibrotic vs non-fibrotic CD lesions; Diagnostic test: stool biomarkers; fecal biomarkers of inflammation, mucosal inflammation; Diagnostic test: MRI imaging; MRI imaging to detect bowel wall fibrosis and to detect inflamed, non-fibrotic from inflamed, fibrotic bowel
Aim 2 Crohn Disease participants (B1 phenotype); Crohn's Disease participants with uncomplicated small bowel disease; No intervention; observational only; collection of blood, stool, and perform MRI; completion of Crohn's Activity Questionnaire	Diagnostic test: blood biomarkers; biomarkers to distinguish fibrotic vs non-fibrotic CD lesions; Diagnostic test: stool biomarkers; fecal biomarkers of inflammation, mucosal inflammation; Diagnostic test: MRI imaging; MRI imaging to detect bowel wall fibrosis and to detect inflamed, non-fibrotic from inflamed, fibrotic bowel
Aim 2 Healthy Controls; No intervention; observational only; collection of blood, stool, and completion of Gastrointestinal Symptoms Rating Scale	Diagnostic test: blood biomarkers; biomarkers to distinguish fibrotic vs non-fibrotic CD lesions; Diagnostic test: stool biomarkers; fecal biomarkers of inflammation, mucosal inflammation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetization transfer ratio (MTR)	compare MTR values between Aim 1 and Aim 2 cohorts	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between MTR values and bowel wall collagen measurements	combine all subjects from Aim 1 and Aim 2 that undergo MRI	Day 1

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Jonathan Dillman, MD, MSc, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): September 1, 2023
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 2019-0677

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