Ulcerative Colitis Clinical Trial
Official title:
Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD
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.
Status | Not yet recruiting |
Enrollment | 230 |
Est. completion date | June 30, 2025 |
Est. primary completion date | May 31, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | N/A and older |
Eligibility | Inclusion Criteria: Clinical diagnosis of COLONIC inflammatory bowel disease (IBD) and non-IBD - COLONIC IBD - Colonic Crohn's disease (Crohn's colitis) - Ulcerative colitis - Indeterminate colitis - COLONIC non-IBD - Diverticulosis - CONTROL - Ileum (positive control) Exclusion Criteria: - Patients with IBD under prescription - Patients with non-colonic IBD - Children |
Country | Name | City | State |
---|---|---|---|
United States | Meharry Medical College | Nashville | Tennessee |
Lead Sponsor | Collaborator |
---|---|
Meharry Medical College |
United States,
Ballard BR, M'Koma AE. Gastrointestinal endoscopy biopsy derived proteomic patterns predict indeterminate colitis into ulcerative colitis and Crohn's colitis. World J Gastrointest Endosc. 2015 Jun 25;7(7):670-4. doi: 10.4253/wjge.v7.i7.670. — View Citation
Korolkova OY, Myers JN, Pellom ST, Wang L, M'Koma AE. Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn's Colitides. Clin Med Insights Gastroenterol. 2015 May 6;8:29-44. doi: 1 — View Citation
M'Koma AE, Seeley EH, Washington MK, Schwartz DA, Muldoon RL, Herline AJ, Wise PE, Caprioli RM. Proteomic profiling of mucosal and submucosal colonic tissues yields protein signatures that differentiate the inflammatory colitides. Inflamm Bowel Dis. 2011 — View Citation
M'Koma AE. Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics. World J Gastrointest Surg. 2014 Nov 27;6(11):208-19. doi: 10.4240/wjgs.v6.i11.208. — View Citation
Rana T, Korolkova OY, Rachakonda G, Williams AD, Hawkins AT, James SD, Sakwe AM, Hui N, Wang L, Yu C, Goodwin JS, Izban MG, Offodile RS, Washington MK, Ballard BR, Smoot DT, Shi XZ, Forbes DS, Shanker A, M'Koma AE. Linking bacterial enterotoxins and alpha — View Citation
Seeley EH, Washington MK, Caprioli RM, M'Koma AE. Proteomic patterns of colonic mucosal tissues delineate Crohn's colitis and ulcerative colitis. Proteomics Clin Appl. 2013 Aug;7(7-8):541-9. doi: 10.1002/prca.201200107. Epub 2013 May 8. — View Citation
Williams AD, Korolkova OY, Sakwe AM, Geiger TM, James SD, Muldoon RL, Herline AJ, Goodwin JS, Izban MG, Washington MK, Smoot DT, Ballard BR, Gazouli M, M'Koma AE. Human alpha defensin 5 is a candidate biomarker to delineate inflammatory bowel disease. PLo — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD | Our two newly developed mAbs will be tested by measuring detection sensitivity specific to peptide DEFA5 protein. DEFA5 detection level between the mAbs will determine the most effective Anti-DEFA5 mAb to be used to develop bioassay kit for DEFA5. | Six months | |
Secondary | Evaluate Established Anti-DEFA5 mAbs Diagnostic Efficacy and Safety in IBD | Using immunohistochemistry (IHC) technology investigators will evaluate diagnostic efficacy and safety of DEFA5 bioassay using colonic IBD biopsies. The DEFA5 protein, which is diagnostic in IBD will be measured and quantified in the colonic biopsies. Investigators will use colon tissue biopsies from patients with UC, CC, IC, diverticulitis, normal (diverticilosis),& ileum as positive control and compare between different pathologies. | 12 months |
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