Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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Biomarkers of Intestinal Fibrosis in Small Bowel Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Diagnostic Test: blood biomarkers
* Diagnostic Test: stool biomarkers
* Diagnostic Test: MRI imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aim 1 (CD participants) Aged 8-70 years Undergoing first surgical distal (ileal) small bowel resection for structuring (B2 phenotype) Crohn's disease as determined by CTE or MRE or ileocolonoscopy English speaking Aim 2 (CD participants) Age 8 to 70 years Uncomplicated inflammatory small bowel CD based on clinical CTE or MRE or ileocolonoscopy performed within 6 months prior to enrollment (CD participants only) English speaking Aim 2 (Control participants) Age 8 to 70 years English speaking Exclusion Criteria: Aim1 (CD participants) B1 or B3 (i.e., fistula, abscess, phlegmon/inflammatory mass) CD phenotype Prior small bowel surgery, including but not limited to surgical resection, stricturoplasty, or endoscopic treatment of a small bowel stricture Anything to eat or drink within 4 hours of study visit (participants may take their required medications with a little water) Known pregnancy (Note: Institutional policies/procedures will be followed for pregnancy screening) Contraindication for MRI (e.g., surgical implant, claustrophobia). Note: To be determined based on local procedures. Aim 2 (CD participants) Stenotic ileocecal valve at colonoscopy Prior small bowel surgery, including but not limited to surgical resection, stricturoplasty, or endoscopic treatment of a small bowel stricture Anything to eat or drink within 4 hours of study visit (participants may take their required medications with a little water) Known pregnancy (Note: Institutional policies/procedures will be followed for pregnancy screening) Contraindication for MRI (e.g., surgical implant, claustrophobia). Note: To be determined based on local procedures. Aim 2 (Control participants) Any known gastrointestinal tract disease Any known inflammatory/autoimmune disease involving another organ system (e.g., rheumatoid arthritis, scleroderma, multiple sclerosis). Fecal calprotectin level of ˃100 mcg.gm will be excluded from further analysis and replaced.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Aim 1 Crohn Disease participants (B2 phenotype)<br>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<br>* biomarkers to distinguish fibrotic vs non-fibrotic CD lesions<br>Diagnostic Test: stool biomarkers<br>* fecal biomarkers of inflammation, mucosal inflammation<br>Diagnostic Test: MRI imaging<br>* MRI imaging to detect bowel wall fibrosis and to detect inflamed, non-fibrotic from inflamed, fibrotic bowel<br>|
| Aim 2 Crohn Disease participants (B1 phenotype)<br>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<br>* biomarkers to distinguish fibrotic vs non-fibrotic CD lesions<br>Diagnostic Test: stool biomarkers<br>* fecal biomarkers of inflammation, mucosal inflammation<br>Diagnostic Test: MRI imaging<br>* MRI imaging to detect bowel wall fibrosis and to detect inflamed, non-fibrotic from inflamed, fibrotic bowel<br>|
| Aim 2 Healthy Controls<br>No intervention; observational only; collection of blood, stool, and completion of Gastrointestinal Symptoms Rating Scale | Diagnostic Test: blood biomarkers<br>* biomarkers to distinguish fibrotic vs non-fibrotic CD lesions<br>Diagnostic Test: stool biomarkers<br>* fecal biomarkers of inflammation, mucosal inflammation<br>|

What is the study measuring?
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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 |