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

Crohn's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02488005
• Other study ID #: GCO 15-0878
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: August 17, 2017

Study information

• Verified date: April 2019
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 17, 2017
• Est. primary completion date: August 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

Device:
• Ultrasound
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

Locations

Country	Name	City	State
United States	Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

Moreno N, Ripollés T, Paredes JM, Ortiz I, Martínez MJ, López 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. — View Citation

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. — View Citation

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, Martín-Comín J, Morana G, Pendsé 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. — View Citation

Paredes JM, Ripollés T, Cortés X, Martínez MJ, Barrachina M, Gómez 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	C-Reactive Protein	C-Reactive Protein (CRP) blood level	14 weeks
Secondary	Change in Erythrocyte Sedimentation Rate (ESR)	Change in Erythrocyte Sedimentation Rate (ESR) blood level at Week 14 from baseline	baseline and 14 weeks
Secondary	IFX Level	Infliximab drug (IFX) level at week 14. normal levels are <0.4 µg/mL	Week 14
Secondary	Anti-infliximab Antibodies (ATI)	Anti-infliximab antibodies at week 14.	Week 14