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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
Sponsor:
Collaborators:
University of California, Davis
University of California, Irvine
University of Chicago
Weill Medical College of Cornell University
Crohn's and Colitis Foundation
Information provided by (Responsible Party):
Glycominds, LLC

Brief Summary:
The purpose of this research study is to determine the efficacy and outcome of the UCRI (an in-vitro diagnostics device in the form of a blood test and an algorithm) as a tool to detect mucosal healing (level of inflammation in the colon) in people with moderate-to-severe ulcerative colitis treated with anti-TNFα. Another reason is to explore additional biomarkers in blood, stool or voice to detect disease activity and/or mucosal healing. A tool to detect the level of inflammation in the colon based on blood, stool or voice biomarkers may reduce the need or the number of invasive endoscopic procedures. This is an observational study and no treatment decision nor clinical intervention will be done based on results during this study and all collected data will be used only for the goal of the study and for obtaining FDA IDE for a follow-up study.

Condition or disease Intervention/treatment
Ulcerative Colitis Diagnostic Test: UCRI

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine



Intervention Details:
  • Diagnostic Test: UCRI
    Biomarker panel and algorithm


Primary Outcome Measures :
  1. UCRI panel validation [ Time Frame: 24 weeks ]
    Accuracy as measured by ROC curve (receiver operating characteristic curve)

  2. UCRI panel validation [ Time Frame: 24 weeks ]
    PPV - Positive Predicative Value: proportions of positive tests that are true positive.

  3. UCRI panel validation [ Time Frame: 24 weeks ]
    NPV - Negative Predicative Value: proportions of negative tests that are true negative.


Secondary Outcome Measures :
  1. 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


Other Outcome Measures:
  1. 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
Whole blood, Serum, Stool


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Subjects will be between the ages of 18 and 65 with a diagnosis of UC and MES = 2 or 3. and intend to start or switch anti-TNFa treatment. Women who are pregnant will also be excluded. Patients who are unable to undergo endoscopic evaluations due to proctitis will also be excluded, as well as patients who have a demonstrated history of steroid refraction. To avoid the 2nd endoscopic assessment time fluctuations patients under anti-TNFa dose escalation or dose adjustment regimen will be excluded.
Criteria

Inclusion Criteria:

  • Ulcerative colitis patients with Mayo Endoscopic Subscore of 2-3
  • Start/switch anti -TNFa treatment
  • Capable of at-home fCal testing

Exclusion Criteria:

  • Pregnant women
  • anti -TNFa dose escalation/adjustment
  • Inability to undergo endoscopic assessments due to Proctitis
  • Diagnosed with infectious diseases
  • Steroid refractory

Information from the National Library of Medicine

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


Contacts
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Contact: Avinoam A Dukler, PhD 8057912094 ext 1 ucri@glycominds.com

Locations
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United States, California
UC Davis Inflammatory Bowel Disease Center Recruiting
Sacramento, California, United States, 95816
Contact: Joshua A Valdez    916-734-8246    joavaldez@ucdavis.edu   
Contact: Joseph B Zepeda    916-734-8985    jlzepeda@ucdavis.edu   
Principal Investigator: Eric J Mao, MD         
Sponsors and Collaborators
Glycominds, LLC
University of California, Davis
University of California, Irvine
University of Chicago
Weill Medical College of Cornell University
Crohn's and Colitis Foundation
Publications:
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Responsible Party: Glycominds, LLC
ClinicalTrials.gov Identifier: NCT04897282    
Other Study ID Numbers: UCRI-1020
First Posted: May 21, 2021    Key Record Dates
Last Update Posted: May 21, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: MES, Treatment, MES, blinded patient characteristics and UCRI and fCal lab results will be shared with researchers.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases