Clinical trial NCT01852760: Assessment of Disease Activity in Ulcerative Colitis by Endoscopic Ultrasound
Official title: Assessment of Disease Activity in Ulcerative Colitis by Endoscopic Ultrasound
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
Inflammatory Bowel Disease
Keywords: endoscopic ultrasound
ulcerative colitis
inflammatory bowel disease
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
name: University of Calgary
name: University of Toronto
name: Dalhousie University
First posted: 2013-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive adult patients with IBD attending outpatient IBD clinics at the University of Western Ontario teaching hospitals and patients admitted to hospital with severe UC will be included for endoscopic ultrasound assessment.

Brief summary: In this cross-sectional study patients with active or quiescent ulcerative colitis will be studied to determine the utility of endoscopic ultrasound measurements of rectal wall blood flow and thickness as reliable indices of disease severity and the degree of correlation that exists with validated clinical, endoscopic, and histological indices.

Detailed description: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown etiology characterized by diffuse mucosal inflammation limited to the colon. The basis of medical treatment is with agents that reduce the inflammatory process. Tailoring appropriate therapy will depend on disease severity, which can be difficult to identify. A response to therapy may also require months to determine. Medications for induction of remission and/or for maintenance in patients with mild to severe UC include 5-aminosalicylates (5'ASA), corticosteroids, azathioprine (AZA), cyclosporine, and infliximab (IFX). All medications have their own inherent side effect profile. Cost can be a major issue with some medications such as IFX, which can be tens of thousands of dollars annually. Medical management can still fail in those with severe disease necessitating surgical management with a colectomy. Identification of high-risk patients who are candidates for more intensive therapy early in the disease course might be a strategy to improve treatment outcomes and limit cost.

This notion of "individualizing" therapy is attractive and a distinct departure from the current "step-care" paradigm in which treatments are added sequentially on the basis of symptom-defined treatment failure. However, for this paradigm to be implementable an objective means of accurately stratifying risk must be identified and validated. Accordingly, increased interest has evolved in the use of biomarkers as prognostic tools. Although fecal calprotectin and serum CRP are potential candidates for this role, these tests have limitations.

Transabdominal ultrasound (US) has been used in the diagnostic workup of IBD. US was a good surrogate of disease activity when compared to colonoscopy, but is unable to reliably assess the rectal wall which tends to cause the most symptoms in UC. Endoscopic ultrasound (EUS) is a highly accurate diagnostic modality for the assessment of rectal pathology. However, the role of EUS in IBD is not well defined. Tsuga et al showed total wall thickness to be highly predictive for acute inflammation in patients with UC compared to healthy controls and that the degree of rectal wall involvement correlated with endoscopic severity. Higaki et al showed patients with quiescent UC who relapsed had initial sonographic evidence of "deep" disease activity shown by significantly greater baseline thickness of the first 3 layers of the rectal wall. Yoshizawa et al subsequently demonstrated that inflammation reaching the muscularis propria or deeper predicted the need for colectomy. Hurlstone et al correlated EUS scores with histopathology, endoscopic, and clinical scores and found good concordance to only exist with superficial EUS scores. In all of these studies the investigators who performed the EUS analysis did so with knowledge of the endoscopy scores. This questions the validity of these results due to the potential for bias. Another parameter that shows promise for evaluation of inflammatory burden is EUS evaluation of blood flow. Surprisingly, Doppler flow has not been used to assess bowel wall vascularity in UC with EUS. We believe that assessment of vascularity has the potential to differentiate with a high degree of accuracy active from quiescent disease.

Although the existing literature indicates that EUS has potential as an evaluative and prognostic tool the investigators believe that a great deal of additional research is needed to further develop this technology. This study will correlate Doppler EUS and other EUS indices with validated clinical, endoscopic, and histological indices of UC inflammation to assess its utility as a diagnostic tool. It will assess the reproducibility of these indices by calculating inter and intra-observer agreement by blinded expert reviewers. This information may have prognostic importance and might ultimately be used to guide therapy in individual patients.

Eligibility criteria: Inclusion Criteria:

* Patients with a confirmed diagnosis of ulcerative colitis aged 18-85
* Patients termed either "active" or "inactive" UC
* Patients may be treatment naïve (ie: new diagnosis) or on existing therapy including 5'ASA (oral or topical), AZA, corticosteroids, or IFX

Exclusion Criteria:

* Inability to or unwillingness to undergo flexible sigmoidoscopy or colonoscopy
* Inability to provide informed consent
* Crohn's disease 4. Presence of an ileoanal pouch

Primary outcomes:
measure: The correlation between EUS indices, clinical, endoscopic, and histological scores of inflammation in UC
timeFrame: 1 day
Secondary outcomes:
measure: Interobserver variability of endoscopic and histologic scores
timeFrame: 1 day
measure: Interobserver variability of EUS Indices
timeFrame: 1 day
measure: Hyperemia score correlation with UC disease activity
timeFrame: 1 day
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care
state: Ontario
Study officials:
affiliation: Western University
name: Brian Yan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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