Utility of Random Biopsies in Patients With Inflammatory Bowel Disease (URBI)

A Randomized Trial of the Utility of Random Biopsies in Patients With Inflammatory Bowel Disease

The proposed study is a multicenter parallel group clinical trial that will include 821 evaluable patients per group who will be randomly assigned to either high definition white light colonoscopy (HDWLC) with targeted biopsies plus 2 random biopsies in 4 segments to assess for inflammation (limited biopsy strategy) or HDWLC with targeted biopsies plus 4 biopsies every 10 cm throughout the colon, at a minimum in all segments of the colon known to have been affected by IBD at any time, regardless of the extent of disease (random biopsy strategy). Participants will be followed until total proctocolectomy or the end of the study period to determine whether the two methods of surveillance colonoscopy are associated with detection of dysplasia or sessile serrated adenoma at follow-up colonoscopy. Follow-up via chart review may continue for up to 15 years from enrollment.

Study Overview

• Status: Enrolling by invitation
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis
• Intervention / Treatment: Other: Biopsy strategy

Detailed Description

To maximize the yield of surveillance colonoscopy, minimize risk to patients, and deliver cost-effective care, it is imperative to resolve whether random biopsies are warranted for patients with long standing Inflammatory Bowel Disease (IBD) undergoing dysplasia and colorectal cancer (CRC) surveillance with high-definition white light colonoscopy (HDWLC). For this protocol, dysplasia surveillance refers to the process of identifying precancerous dysplasia, sessile serrated adenoma (SSA) or CRC. This protocol describes a pragmatic, multicenter randomized trial of patients with IBD undergoing dysplasia surveillance with HDWLC, the most common type of surveillance colonoscopy performed in the US, to definitively answer this question.

The primary objective of the study is to determine if HDWLC using a limited biopsy strategy is non-inferior to HDWLC using a random biopsy strategy to detect dysplasia or sessile serrated adenoma (SSA) in patients with IBD.

Secondary objectives include:

1. Determine if HDWLC using a limited biopsy strategy is superior to HDWLC with a random biopsy strategy to detect one or more dysplastic or SSA lesion in patients with IBD
2. Determine whether the number of targeted biopsies differs based on the number of random biopsies obtained.

• Study Type: Interventional
• Enrollment (Estimated): 1642
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • San Diego, California, United States, 92121
      • Scripps Health
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32804
      • AdventHealth
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15224
      • Allegheny Health Network
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of left-sided (greater than 15 cm of disease but not beyond the splenic flexure) or extensive (extending beyond the splenic flexure) ulcerative colitis or IBD-U or colonic Crohn's disease involving at least 1/3 of the colon (defined as 2 segments of the remaining colon; segments include right colon, transverse colon, left colon and rectum).

• Disease duration must meet one of the following criteria:

  1. onset of symptoms of IBD at least 8 years prior
  2. diagnosis of IBD at least 8 years prior
  3. diagnosis of IBD for any duration if other risk factors for colon cancer are present including: concomitant diagnosis of primary sclerosing cholangitis, personal history of dysplasia, sessile serrated adenoma or right sided hyperplastic polyps greater than 10mm in diameter, or a family history of colon cancer in a first degree relative or two second degree relatives.
• Scheduled to undergo colonoscopy as part of routine care
• At least one indication for the index colonoscopy must be to perform dysplasia surveillance.

Exclusion Criteria:

• Any condition that the endoscopist feels is a contraindication to random biopsies
• History of visible (high or low grade) dysplasia not completely removed
• History of sessile serrated adenoma not completely removed
• History of colorectal cancer
• Any condition for which the endoscopist feels that pancolonic contrast or virtual chromoendoscopy is mandatory
• Less than 2 segments of the remaining colon have ever been involved with IBD

• Colonoscopy* in the last 11 months unless the colonoscopy:

  1. was determined by the endoscopist to be insufficient for dysplasia surveillance and,
  2. did not include a diagnosis of dysplasia or sessile serrated adenoma. *Does not include sigmoidoscopy
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Limited biopsy strategy; Targeted biopsies plus 2 random biopsies in 2 segments to assess for inflammation	Other: Biopsy strategy; Number of random biopsies, in addition to targeted biopsies, taken during colonoscopies where at least one indication for the colonoscopy is surveillance for dysplasia
Active Comparator: Random biopsy strategy; Targeted biopsies plus 4 biopsies every 10 cm throughout the colon, at a minimum in all segments of the colon known to have been affected by IBD at any time	Other: Biopsy strategy; Number of random biopsies, in addition to targeted biopsies, taken during colonoscopies where at least one indication for the colonoscopy is surveillance for dysplasia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of dysplastic or SSA lesions detected per colonoscopy	The rationale for this as the primary outcome is that it is important to detect and remove all precancerous lesions. For this outcome, the investigators will include low grade dysplasia (LGD), high grade dysplasia (HGD), SSA or CRC but not indefinite for dysplasia (IFD). Dysplasia will include both conventional and nonconventional forms of dysplasia. Although SSAs do not typically have histologic changes of dysplasia, they are considered precancerous lesions and are more difficult to detect than sporadic adenomatous polyps. The number of dysplastic or SSA lesions will be defined as the number of pathology jars containing a specimen with low-grade or high-grade dysplasia (including CRC) or serrated changes consistent with a sessile serrated adenoma-like change. Even if there are more than one biopsy sample in a jar with dysplasia or SSA, it will be counted as one location with dysplasia or SSA.	At index colonoscopy

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: James D Lewis, MD, MSCE, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: colonoscopy; IBD; Crohn's disease; ulcerative colitis; UC; inflammatory bowel diseases; random biopsies
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Colitis; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases
• Other Study ID Numbers: 15225; U01DK138901 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No