Ultrasound Stiffness Imaging in Crohn's Disease

Crohn's Disease Clinical Trial

Official title:

Investigating Ultrasound Stiffness Imaging for Predicting Outcomes in Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01666626
• Other study ID #: HUM64431
• Status: Completed
• Phase: N/A
• First received: August 7, 2012
• Last updated: July 29, 2015
• Start date: September 2012
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to determine whether ultrasound-based assessment of intestinal stiffness in patients with Crohn's disease predicts the effectiveness of medical therapy or the need for surgical resection.

Description:

Modern medical therapy in Crohn's disease, including immunomodulators and biologic compounds, has revolutionized disease treatment. However, a significant portion of individuals will not respond to medications, most often due to the development of intestinal fibrosis. Over the course of Crohn's disease repeated episodes of inflammation and abnormal wound healing lead to progressive intestinal fibrosis, strictures, and bowel obstruction. While inflammatory Crohn's disease often responds to medical therapy, predominantly fibrostenotic intestinal disease is unresponsive and requires surgery. Our inability to accurately distinguish intestinal inflammation from fibrosis frequently leads to empiric trials of steroids and immunosuppressive therapies. This often proves futile, delays inevitable surgery, and unnecessarily exposes the patient to medication-related risks for months and sometimes years. At present there are no available means to distinguish medically responsive inflammatory disease from predominately fibrotic intestinal disease. The unmet need in this field is an accurate diagnostic technology to determine which patients will benefit from anti-inflammatory therapy, and which patients should go directly to surgery. Non-invasive ultrasound stiffness imaging (USI) may be a surrogate marker of underlying bowel wall fibrosis that aids in predicting if Crohn's disease will be responsive to medical therapy.

Two USI methods have recently been developed: Ultrasound elasticity imaging (UEI) uses 2D speckle-tracking to measure tissue strain, a surrogate of fibrosis. The second, shear wave imaging (SWI), is a commercially available technology that measures the speed of ultrasonic shear waves through tissue. Shear waves travel more rapidly through stiff tissue. The central hypothesis of this proposal is that ultrasound stiffness imaging (USI) quantitatively distinguishes predominately inflammatory from fibrotic bowel wall thickening, and therefore is predictive of the likelihood of response to medical therapy or the need for surgery.

We plan to objectively test our central hypothesis and attain the objective of this application by pursuing the following three specific aims:

Specific Aim 1 (SA-1): Determine if USI stiffness measurements of intestinal strictures in Crohn's patients admitted with small bowel obstruction predicts response or failure of medical therapy based on CDAI and objective inflammatory biomarkers during index hospitalization and at 90 day follow-up.

Inpatient Inclusion Criteria:

• Subjects must be 18 years of age or older

• Previous diagnosis of Crohn's disease with imaging demonstrating involvement of the ileum

• Hospital admission imaging demonstrating small bowel dilation (to > 3.5 cm)

• CDAI score of >220.

Inpatient Exclusion Criteria:

• Active Clostridium difficile colitis/enteritis

• Presence of abdominal enterocutaneous fistulas in the ultrasound path.

• Prior abdominal hernia repair with mesh placement in the ultrasound path.

Specific Aim 2 (SA-2): Determine if USI stiffness measurements of diseased ileum in Crohn's outpatients starting Anti-Tumor Necrosis Factor-Alpha therapy predicts response to medical therapy based on CDAI and objective inflammatory biomarkers.

Outpatient Inclusion Criteria

• Crohn's patients age 18 and over starting anti-TNF therapy

• CDAI score > 220 to denote clinical disease activity.

Outpatient Exclusion Criteria:

• Active Clostridium difficile colitis/enteritis

• Presence of abdominal enterocutaneous fistulas in the ultrasound path

• Prior abdominal hernia repair with mesh placement in the ultrasound path

• Current use of prednisone or budesonide

• Changing anti-TNF due to allergy (including a TNF-induced lupus-like arthritis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• CDAI score >220

• if INPATIENT: admission for small bowel obstruction.

• if OUTPATIENT: start of anti-tumor necrosis alpha therapy

Exclusion Criteria:

• Active Clostridium difficile colitis/enteritis

• Presence of abdominal enterocutaneous fistulas in the ultrasound path

• Prior abdominal hernia repair with mesh placement in the ultrasound path

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Acoustic Radiation Force Impulse
• Crohn Disease
• Crohn's Disease
• Intestinal Fibrosis
• Shear Wave Imaging
• Ultrasound

Intervention

Procedure:
• Ultrasound stiffness imaging
Subjects will undergo transabdominal ultrasound of the distal intestine. Distal intestine motion capture will be used for off-line stiffness assessment by two-dimensional speckle tracking. In addition, shear wave imaging will be used for real-time stiffness assessment.

Locations

Country	Name	City	State
United States	University of Michigan Health System	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Crohn's and Colitis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CDAI Score Over 90 days from Hospital Admission	CDAI score will be assessed at 3 time points: Hospital Admission Hospital Discharge 90-day follow-up	CDAI Score measured over 90 days	No
Primary	Shear Wave Velocity	Ultrasound shear wave velocity measurements in bowel wall	Day 0,3,5,7 of Hospitalization	No
Secondary	Need for Re-hospitalization or Surgery within 90 days of discharge	Telephone follow up with subjects 90 days following index hospitalization to assess need for re-hospitalization or surgery	90 days post discharge	No