The Use of Small Bowel Ultrasound to Predict Response to Remicade Induction

Study Overview
=================
Brief Summary
-----------------
Small bowel ultrasound (SBUS) is emerging as a well tolerated, non-invasive, radiation free, low cost measure to assess inflammatory bowel disease (IBD), and is being used as first-line imaging in Europe. SBUS findings have been shown to correlate with endoscopic findings, and a small number of recent studies have looked at change in bowel wall thickness (BWT) in response to anti-tumor necrosis factor (anti-TNF) therapy. However, the use of SBUS to detect response to anti-TNF therapy has not been tested in pediatric patients. The purpose of this study is to apply the use of SBUS to pediatric patients with Crohn's disease and to assess response to treatment with infliximab. The investigators will also measure C-reactive protein and fecal calprotectin at baseline, and additionally measuring IFX levels and anti-infliximab antibodies (ATI) at week 14 to assess change in biochemical response to infliximab treatment, as well as correlation between these markers with changes in patient reported outcomes via a weighted pediatric Crohn's disease activity questionnaire (wPCDAI) and changes in BWT. This study is novel in that it will be the first study in pediatric patients to use SBUS to assess response to IFX therapy, and will also be the first study to correlate SBUS findings with therapeutic drug monitoring (TDM). This study has the potential to propagate the use of SBUS in the pediatric population, as the use of TDM in concert with small bowel imaging post-induction will allow the investigators to tailor therapy early in the treatment course.

Detailed Description
-----------------
Pediatric inflammatory bowel disease (IBD) patients are at increased risk for high ionizing radiation exposure in the assessment of their condition. Small bowel ultrasound (SBUS) is emerging as a well tolerated, non-invasive, radiation free, low cost measure to assess inflammatory bowel disease, and is being used as first-line imaging in Europe. SBUS findings have been shown to correlate with endoscopic findings, and a small number of recent studies have looked at change in bowel wall thickness (BWT), in response to anti-TNF therapy. The use of SBUS to detect response to anti-TNF therapy has not been tested in pediatric patients. In addition, these studies frequently use Crohn's Disease Activity Index (CDAI) as a measure of clinical activity, yet it is known from multiple studies including the SONIC trial that CDAI is not a reliable or accurate measure to predict mucosal healing. A weighted PCDAI will be used instead, which has been shown to perform better than the original PCDAI and is more feasible, especially considering the study spans 14 weeks and scoring items such as height velocity from the full PCDAI will be irrelevant. The goal of this study is to measure bowel wall thickness (BWT) prior to initiating infliximab (IFX 0) and at week 14 and to look at the correlation between change in BWT (delta BWT) with change in clinical disease activity (delta wPCDAI) between these two time points. The research team will measure fecal calprotectin at baseline and at week 14 with stool collected the day prior to the visit using a specimen collection kit given to subjects. The research team will also collect results from routine laboratories (including C-Reactive Protein, Erythrocyte Sedimentation Rate, Complete Blood Count, and Albumin) done before each infusion, and IFX levels and anti-infliximab antibodies (ATI) at week 14 to assess change in biochemical response to infliximab treatment, as well as correlation between these markers with changes in patient reported outcomes (via a wPCDAI questionnaire) and changes in BWT.

Official Title
-----------------
The Use of Small Bowel Ultrasound to Predict Response to Remicade Induction

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Device: Ultrasound


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: No infliximab therapy previously initiated Infliximab indicated for treatment of IBD Patient consent/assent and/or parent/guardian consent Ability to remain in follow-up for 14 weeks from start of study Exclusion Criteria: Lack of small bowel disease Inability to give consent or adhere to study protocol Infliximab-experienced Presence of active infections Presence of abscess or strictures Current or planned Pregnancy for the 14 week study duration

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Small Bowel Ultrasound<br>Subjects will receive a small bowel ultrasound to measure bowel wall thickness at Week 0 and Week 14 | Device: Ultrasound<br>* An ultrasound of the small bowel will be done by a radiologist or ultrasound technician. Subject should not eat or drink anything (i.e. no food and no water/beverages) for 8 hours prior to their ultrasound appointment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bowel Wall Thickness (BWT) | Change in Bowel Wall Thickness at week 14 as compared to baseline, prior to initiating infliximab (IFX 0). | Baseline and Week 14 | 
| Change in Weighted Pediatric Crohn's Disease Activity Index (wPCDAI) | wPCDAI at week 14 as compared to baseline. PCDAI includes three history items (abdominal pain, number of liquid stools, general wellbeing), five physical examination items (abdominal examination, perirectal disease, extraintestinal manifestations, weight, height), and three laboratory tests (hematocrit, albumin, erythrocyte sedimentation rate). Items are scored on a three-point scale (zero, 5, or 10 points) except for hematocrit and erythrocyte sedimentation rate which are scored as zero, 2.5 or 5 points. PCDAI scores can range from zero to 125 with higher scores indicating more active disease. | Baseline and Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fecal Calprotectin | change in fecal calprotectin at week 14 compared to baseline, using a specimen collection kit given to subjects | Baseline and Week 14 | 
| C-Reactive Protein | C-Reactive Protein (CRP) blood level | 14 weeks | 
| Change in Erythrocyte Sedimentation Rate (ESR) | Change in Erythrocyte Sedimentation Rate (ESR) blood level at Week 14 from baseline | baseline and 14 weeks | 
| IFX Level | Infliximab drug (IFX) level at week 14. normal levels are <0.4 µg/mL | Week 14 | 
| Anti-infliximab Antibodies (ATI) | Anti-infliximab antibodies at week 14. | Week 14 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inflammatory Bowel Disease, Small Bowel, Crohn's Disease, Small Bowel Ultrasound