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

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.

Conditions

• Inflammatory Bowel Diseases
• Ulcerative Colitis
• Crohn Colitis
• Indeterminate Colitis

Interventions

DIAGNOSTIC_TEST

Diagnostic Test

30% of IBD patients are misdiagnosed. This affects surgical care of patients. Investigators have unveiled a signature discriminator between UC\&CC that also predicts the outcome of IC patients into authentic UC/CC. This is a bioassay that is specific, sensitive, linear, affordable, minimal risk, non-invasive and constitutes an inexpensive, simple to use, point-of-care test format. Investigators published data which have shown robust presence of DEFA5 in the colon crypt mucosa with aberrant expression of apparent crypt-cell-like cells (CCLCs) in areas identified with ectopic colon ileal metaplasia consistent with CC. Investigators propose to validate that UC/CC, the two unsolved medical sub-types of pathology can accurately be distinguished among IC patients by examining CCLCs secreted DEFA5 levels in endoscopy biopsies instantly. Diagnostics relies on the expression/localization/activation of DEFA5 and the ectopic CCLCs in the mucosal crypt of CC patients.

Sponsors & Collaborators

• Meharry Medical College

  lead OTHER

Principal Investigators

• Amosy E M'Koma, MD, MS, PhD · Meharry Medical College

Eligibility

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-06-01

Primary Completion

2025-05-31

Completion

2025-06-30

Countries

• United States

Study Locations