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

NCT02488005 | Completed Results

• 1 other identifier: GCO 15-0878
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn's Disease

Keywords

Inflammatory Bowel Disease; Small Bowel; Crohn's Disease; Small Bowel Ultrasound

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Change in Fecal Calprotectin

  Baseline and Week 14

• C-Reactive Protein

  14 weeks

• Change in Erythrocyte Sedimentation Rate (ESR)

  baseline and 14 weeks

• IFX Level

  Week 14

• Anti-infliximab Antibodies (ATI)

  Week 14

Study Arms (1)

Small Bowel Ultrasound

EXPERIMENTAL

Subjects will receive a small bowel ultrasound to measure bowel wall thickness at Week 0 and Week 14

Device: Ultrasound

Interventions

Ultrasound DEVICE

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

Small Bowel Ultrasound

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center

New York, New York, 10029, United States

Location

Related Publications (10)

• Sauer CG, Kugathasan S, Martin DR, Applegate KE. Medical radiation exposure in children with inflammatory bowel disease estimates high cumulative doses. Inflamm Bowel Dis. 2011 Nov;17(11):2326-32. doi: 10.1002/ibd.21626. Epub 2011 Jan 13.

  PMID: 21987300 BACKGROUND

• Panes J, Bouhnik Y, Reinisch W, Stoker J, Taylor SA, Baumgart DC, Danese S, Halligan S, Marincek B, Matos C, Peyrin-Biroulet L, Rimola J, Rogler G, van Assche G, Ardizzone S, Ba-Ssalamah A, Bali MA, Bellini D, Biancone L, Castiglione F, Ehehalt R, Grassi R, Kucharzik T, Maccioni F, Maconi G, Magro F, Martin-Comin J, Morana G, Pendse D, Sebastian S, Signore A, Tolan D, Tielbeek JA, Weishaupt D, Wiarda B, Laghi A. Imaging techniques for assessment of inflammatory bowel disease: joint ECCO and ESGAR evidence-based consensus guidelines. J Crohns Colitis. 2013 Aug;7(7):556-85. doi: 10.1016/j.crohns.2013.02.020. Epub 2013 Apr 11.

  PMID: 23583097 BACKGROUND

• Calabrese E, Zorzi F, Zuzzi S, Ooka S, Onali S, Petruzziello C, Lasinio GJ, Biancone L, Rossi C, Pallone F. Development of a numerical index quantitating small bowel damage as detected by ultrasonography in Crohn's disease. J Crohns Colitis. 2012 Sep;6(8):852-60. doi: 10.1016/j.crohns.2012.01.015. Epub 2012 Feb 23.

  PMID: 22398077 BACKGROUND

• Onali S, Calabrese E, Petruzziello C, Zorzi F, Sica GS, Lolli E, Ascolani M, Condino G, Pallone F, Biancone L. Endoscopic vs ultrasonographic findings related to Crohn's disease recurrence: a prospective longitudinal study at 3 years. J Crohns Colitis. 2010 Sep;4(3):319-28. doi: 10.1016/j.crohns.2009.12.010. Epub 2010 Feb 19.

  PMID: 21122521 BACKGROUND

• Zorzi F, Stasi E, Bevivino G, Scarozza P, Biancone L, Zuzzi S, Rossi C, Pallone F, Calabrese E. A sonographic lesion index for Crohn's disease helps monitor changes in transmural bowel damage during therapy. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2071-7. doi: 10.1016/j.cgh.2014.04.036. Epub 2014 May 6.

  PMID: 24813174 BACKGROUND

• Castiglione F, Testa A, Rea M, De Palma GD, Diaferia M, Musto D, Sasso F, Caporaso N, Rispo A. Transmural healing evaluated by bowel sonography in patients with Crohn's disease on maintenance treatment with biologics. Inflamm Bowel Dis. 2013 Aug;19(9):1928-34. doi: 10.1097/MIB.0b013e31829053ce.

  PMID: 23835441 BACKGROUND

• Moreno N, Ripolles T, Paredes JM, Ortiz I, Martinez MJ, Lopez A, Delgado F, Moreno-Osset E. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies. J Crohns Colitis. 2014 Sep;8(9):1079-87. doi: 10.1016/j.crohns.2014.02.008. Epub 2014 Mar 7.

  PMID: 24613399 BACKGROUND

• Paredes JM, Ripolles T, Cortes X, Martinez MJ, Barrachina M, Gomez F, Moreno-Osset E. Abdominal sonographic changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn's Disease. Dig Dis Sci. 2010 Feb;55(2):404-10. doi: 10.1007/s10620-009-0759-7. Epub 2009 Mar 7.

  PMID: 19267199 BACKGROUND

• Turner D, Griffiths AM, Walters TD, Seah T, Markowitz J, Pfefferkorn M, Keljo D, Waxman J, Otley A, LeLeiko NS, Mack D, Hyams J, Levine A. Mathematical weighting of the pediatric Crohn's disease activity index (PCDAI) and comparison with its other short versions. Inflamm Bowel Dis. 2012 Jan;18(1):55-62. doi: 10.1002/ibd.21649. Epub 2011 Feb 23.

  PMID: 21351206 BACKGROUND

• 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.

  PMID: 32453126 DERIVED

MeSH Terms

Conditions

Crohn Disease; Inflammatory Bowel Diseases

Interventions

Ultrasonography

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Limitations and Caveats

Small sample size.

Results Point of Contact

• Title: Becky Phan
• Organization: Icahn School of Medicine at Mount Sinai

becky.phan@mssm.edu

212-824-7785

Study Officials

• Marla C. Dubinsky, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2015
• First Posted: July 2, 2015
• Study Start: April 1, 2016
• Primary Completion: August 17, 2017
• Study Completion: August 17, 2017
• Last Updated: May 10, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-04

Locations

US (1)