Prospective Multicenter Trial to Determine the Efficacy and Outcome of the UCRI Biomarker Panel and Algorithm to Detect Mucosal Healing in Moderate to Severe Ulcerative Colitis Patients.
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|ClinicalTrials.gov Identifier: NCT04897282|
Recruitment Status : Recruiting
First Posted : May 21, 2021
Last Update Posted : May 21, 2021
|Condition or disease||Intervention/treatment|
|Ulcerative Colitis||Diagnostic Test: UCRI|
At the early stage of mucosal inflammation in patients with inflammatory Bowel Diseases (IBD), neutrophils flood into intestinal mucosa, phagocytose pathogenic microbes, and promote mucosal healing and resolution of inflammation. However, large numbers of neutrophils infiltrating in the inflamed mucosa and accumulating in the epithelium cause damage of mucosal architecture, compromised epithelial barrier and production of inflammatory mediators. Novel neutrophil-related serum markers are emerging in the literature and are valid candidates to surrogate markers for mucosal healing (MH). NGAL is an anti-bacterial protein, whereas MMP-9 is a protein with enzymatic activity towards extracellular matrix (ECM) and non-ECM components, and is involved in cell signaling.
By formation of a complex between NGAL and MMP-9, NGAL is thought to protect MMP-9 from autodegradation. Cathelicidin LL37 is the 37 amino acids C-terminal part of human cationic antimicrobial protein (hCAP)18 and acts as an antimicrobial protein (AMP). It is found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs) as well as keratinocytes and plays a role in the early host response against invading pathogens via its broad-spectrum anti-microbial activity. The expression of LL37 was found to be increased in the inflamed mucosa of patients with UC and CD3. Moreover, increased colonic LL37 expression in macrophages and epithelium was observed during colitis in UC patients. Chitinase 3 like 1 (CHI3L1), also known as YKL-40, is a 39 kDa secreted glycoprotein member of the glycosyl hydrolase 18 family although it does not show chitotriosidase activity. It is secreted by macrophages and neutrophils and acts as a growth factor for vascular endothelial cells and fibroblasts.
In previous retrospective single-site study, consisting of serum samples and endoscopic evaluation before and after anti-TNFa treatment from 176 moderate-to-severe UC patients and 75 healthy controls, showed that the combined use of these markers is statistically significant and can accurately correlate with the Mayo endoscopic subscore (MES) and identify endoscopic response to infliximab (IFX) and adalimumab (ADM. An algorithm, the Ulcerative Colitis Response Index (UCRI), a unit-less index ranging from 0 (likely a responder) to 10 (likely a non-responder) was constructed and identified accentually the anti-TNFa non-responders' patients as measured by endoscopic assessment MES ≥2.
Glycominds, LLC (the "Sponsor") in support of the Crohn's and Colitis Foundation (CCF) IBD Venture will conduct this prospective multicenter longitudinal study in the U.S. Following screening and patient enrollment based on the inclusion and exclusion criteria Imaging, blood (serum) and fecal samples will be collected at certain predefined time points from bio naïve (naïve) and from anti-TNFa previously exposed (exposed) active (MES >2) UC patients that will start an anti-TNFa treatment or switch from one anti-TNFa type to another (infliximab-IFX or biosimilars, adalimumab-ADM, golimumab-GOM) at time of recruitment. Collected blood and stool samples will be used to determine the accuracy and prediction value of the UCRI biomarker panel and algorithm in comparison with endoscopic healing (measured as end point of MES ≤ 2) and in comparison to fecal Calprotectin. The IFX/ADM/GOM treatment decision and endoscopic evaluations before and after treatment initiation/switching will be done according to current clinical practice and Sponsor will not have any influence or responsibilities on those decisions.
|Study Type :||Observational|
|Estimated Enrollment :||100 participants|
|Official Title:||Prospective Multicenter Trial to Determine the Efficacy and Outcome of the UCRI In-vitro Diagnostics Device to Detect Treatment Response Measured by Endoscopic Healing in Moderate to Severe Ulcerative Colitis Patients Treated With Anti-TNF-a.|
|Estimated Study Start Date :||May 24, 2021|
|Estimated Primary Completion Date :||November 30, 2022|
|Estimated Study Completion Date :||December 31, 2022|
- Diagnostic Test: UCRI
Biomarker panel and algorithm
- UCRI panel validation [ Time Frame: 24 weeks ]Accuracy as measured by ROC curve (receiver operating characteristic curve)
- UCRI panel validation [ Time Frame: 24 weeks ]PPV - Positive Predicative Value: proportions of positive tests that are true positive.
- UCRI panel validation [ Time Frame: 24 weeks ]NPV - Negative Predicative Value: proportions of negative tests that are true negative.
- fCal comparison analysis [ Time Frame: 24 weeks ]As a secondary outcome a comparison analysis with fecal Calprotectin (fCal) at 250 ug/g cut-off value will be performed
- UCRI prediction value [ Time Frame: 0-14 weeks ]The UCRI prediction value as survival analysis (longrank tests) of MES following anti-TNFa treatment. Event will be defined as MES<2
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04897282
|Contact: Avinoam A Dukler, PhD||8057912094 ext firstname.lastname@example.org|
|United States, California|
|UC Davis Inflammatory Bowel Disease Center||Recruiting|
|Sacramento, California, United States, 95816|
|Contact: Joshua A Valdez 916-734-8246 email@example.com|
|Contact: Joseph B Zepeda 916-734-8985 firstname.lastname@example.org|
|Principal Investigator: Eric J Mao, MD|