Brief Summary

Investigators propose to validate efficacy and safety of the detection of DEFA5 in the diagnosis of the colonic IBD using longitudinal vs. cross-sectional studies of known patient clinical data to correlate with their endoscopy biopsy data. 30% of colonic IBD patients cannot be accurately diagnosed (CC vs. UC) in a timely manner even when a state-of-the-art classification system of combined clinical, endoscopic, radiologic and histologic tools are used. When the diagnostic classification for these two diseases is inconclusive, the condition is termed indeterminate colitis (IC). Here, the central medical challenge is the discrimination of IBD into the specific subtypes with high accuracy, as it greatly effects surgical care of patients. Diagnostic accuracy of IC into either authentic UC or CC is of utmost importance when determining a patient's candidacy for RPC-IPAA surgery, the standard curative surgical procedure for UC. Further, incorrect diagnosis and treatment carry potential morbidity from inappropriate and unnecessary surgery and costs. The success outcomes of RPC-IPAA surgery and convalescence depend on correct diagnosis. To address IBD diagnosis ambiguity and delays in IBD clinical settings, investigators developed a proteomic signature to discriminate between UC and CC patients that also will predict the outcome of IC patients for their eventual progress to either UC or CC. Our published data has shown robust evidence supporting presence of human alpha-defensin 5 (DEFA5) in areas of the colon mucosa with aberrant expression of apparent Paneth cell-like cells (PCLCs) or crypt cell-like cells (CCLCs), which identifies an area of colonic ileal metaplasia, consistent with the diagnosis of CC. DEFA5 bioassay discriminated CC and UC in a cohort of all IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96%. These findings were obtained solely from colectomy specimens for both the discovery and validation analyses. Investigators believe that use of endoscopy biopsies would be indifferent, which is the purpose of this prospective patient centered clinical study. Investigators propose to demonstrate that UC and CC, the two unsolved medical subtypes of pathology with no drugs for a cure, can accurately be distinguished molecularly by examining CCLCs-secreted DEFA5 in colonic endoscopy biopsies instantly. Our proposal is highly innovative, as it highlights the robustness of DEFA5 and its clinical relevance to IBD is both in science and the anticipated impact, as investigators seek to better understand difficulty to determine 'subtypes" and translate that to improve diagnosis, treatment, clinical outcomes, and quality of life for patients and the realm of clinical care. DEFA5 immunoreactivity in colonic endoscopy biopsies could be a rapid potential diagnostic signature to resolve IC into authentic UC and CC with a first clinic endoscopy biopsy. IC is likely to be eliminated for good.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

230

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started Jun 2023

Typical duration for all trials

Geographic Reach

1 country

1 active site

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

2.1 years study duration

First Submitted

Initial submission to the registry

November 15, 2022

Completed

1 month until next milestone

First Posted

Study publicly available on registry

December 23, 2022

Completed

5 months until next milestone

Study Start

First participant enrolled

June 1, 2023

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2025

Completed

1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2025

Completed

Last Updated

December 23, 2022

Status Verified

December 1, 2022

Enrollment Period

2 years

First QC Date

November 15, 2022

Last Update Submit

December 15, 2022

Conditions

Inflammatory Bowel Diseases Ulcerative Colitis Crohn Colitis Indeterminate Colitis

Keywords

Inflammatory bowel diseaseCrohn's colitisUlcerative colitisIndeterminate colitisDEFA5Molecular diagnosticsColonic biopsies

Outcome Measures

Primary Outcomes (1)

Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD
Using Western blot (WB) technology investigators will evaluate our newly established Anti-DEFA5 mAbs by measuring and quantifying DEFA5 protein levels in colonic biopsies from IBD and non-IBD patients. Anti-DEFA5 monoclonal antibodies (mAbs), i.e., clones 1A8 \& 4FD efficacy. Anti-DEFA5 mAbs specificity and sensitivity to the DEFA5 protein which is diagnostic for colonic Crohn's disease
Six moths

Secondary Outcomes (2)

Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD
Six months
Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD
12 months

Study Arms (5)

Crohn's colitis

Correlate patient longitudinal study of clinical data and their biopsy data. Investigators will determine DEFA5 levels from endoscopy biopsies from known authentic CC patients.