Clinical trial NCT02488005: The Use of Small Bowel Ultrasound to Predict Response to Remicade Induction
Official title: The Use of Small Bowel Ultrasound to Predict Response to Remicade Induction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Keywords: Inflammatory Bowel Disease
Small Bowel
Crohn's Disease
Small Bowel Ultrasound
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2015-07-02
Enrollment: 15
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Change in Bowel Wall Thickness (BWT)
timeFrame: Baseline and Week 14
measure: Change in Weighted Pediatric Crohn's Disease Activity Index (wPCDAI)
timeFrame: Baseline and Week 14
Secondary outcomes:
measure: Change in Fecal Calprotectin
timeFrame: Baseline and Week 14
measure: C-Reactive Protein
timeFrame: 14 weeks
measure: Change in Erythrocyte Sedimentation Rate (ESR)
timeFrame: baseline and 14 weeks
measure: IFX Level
timeFrame: Week 14
measure: Anti-infliximab Antibodies (ATI)
timeFrame: Week 14
Other outcomes:
Locations:
city: New York
country: United States
facility: Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Marla C. Dubinsky, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Dolinger MT, Choi JJ, Phan BL, Rosenberg HK, Rowland J, Dubinsky MC. Use of Small Bowel Ultrasound to Predict Response to Infliximab Induction in Pediatric Crohn's Disease. J Clin Gastroenterol. 2021 May-Jun 01;55(5):429-432. doi: 10.1097/MCG.0000000000001367.