Clinical trial NCT01666626: Ultrasound Stiffness Imaging in Crohn's Disease
Official title: Investigating Ultrasound Stiffness Imaging for Predicting Outcomes in Crohn's Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Crohn's Disease
Ultrasound
Intestinal Fibrosis
Shear Wave Imaging
Acoustic Radiation Force Impulse
Keywords: crohn's disease
ultrasound
intestinal fibrosis
shear wave imaging
acoustic radiation force impulse
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2012-08-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with Crohn's disease, either:

* hospitalized for small bowel obstruction, OR,
* undergoing outpatient start of anti-tumor necrosis factor alpha

Brief 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in CDAI Score Over 90 days from Hospital Admission
timeFrame: CDAI Score measured over 90 days
measure: Shear Wave Velocity
timeFrame: Day 0,3,5,7 of Hospitalization
Secondary outcomes:
measure: Need for Re-hospitalization or Surgery within 90 days of discharge
timeFrame: 90 days post discharge
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
Study officials:
affiliation: University of Michigan
name: Ryan W Stidham, MD
role: PRINCIPAL_INVESTIGATOR
References: