Ulcerative ColitisNCT04897282
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.
An observational study of Ulcerative Colitis, run by Glycominds, LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- UCRI
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2021to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Ulcerative colitis patients with Mayo Endoscopic Subscore of 2-3
- Start/switch anti -TNFa treatment
- Capable of at-home fCal testing
Who cannot join
- Pregnant women
- anti -TNFa dose escalation/adjustment
- Inability to undergo endoscopic assessments due to Proctitis
- Diagnosed with infectious diseases
- Steroid refractory
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
UC Davis Inflammatory Bowel Disease Center
Sacramento, California, 95816
Joshua A Valdez, 916-734-8246, joavaldez@ucdavis.edu
Joseph B Zepeda, 916-734-8985, jlzepeda@ucdavis.edu
About this study
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.
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- UCRI
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UCRIDiagnostic test
Biomarker panel and algorithm
What is being measured
The primary outcome is the main question the study is designed to answer.
UCRI panel validation
Accuracy as measured by ROC curve (receiver operating characteristic curve)
Measured: 24 weeks
UCRI panel validation
PPV - Positive Predicative Value: proportions of positive tests that are true positive.
Measured: 24 weeks
UCRI panel validation
NPV - Negative Predicative Value: proportions of negative tests that are true negative.
Measured: 24 weeks
Secondary outcomes (1)
fCal comparison analysis
As a secondary outcome a comparison analysis with fecal Calprotectin (fCal) at 250 ug/g cut-off value will be performed
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2021
- Study start24 Aug 2021
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Glycominds, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of California, Davis, University of California, Irvine, University of Chicago, Weill Medical College of Cornell University, Crohn's and Colitis Foundation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04897282
- Sponsor's protocol ID
- UCRI-1020
- Status last verified
- Aug 2023
- First submitted
- 26 Apr 2021
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: MES, Treatment, MES, blinded patient characteristics and UCRI and fCal lab results will be shared with researchers.
Publications
de Bruyn M, Ringold R, Martens E, Ferrante M, Van Assche G, Opdenakker G, Dukler A, Vermeire S. The Ulcerative Colitis Response Index for Detection of Mucosal Healing in Patients Treated With Anti-tumour Necrosis Factor. J Crohns Colitis. 2020 Feb 10;14(2):176-184. doi: 10.1093/ecco-jcc/jjz125.
PubMed 31628842Koon HW, Shih DQ, Chen J, Bakirtzi K, Hing TC, Law I, Ho S, Ichikawa R, Zhao D, Xu H, Gallo R, Dempsey P, Cheng G, Targan SR, Pothoulakis C. Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology. 2011 Nov;141(5):1852-63.e1-3. doi: 10.1053/j.gastro.2011.06.079. Epub 2011 Jul 14.
PubMed 21762664
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04897282
- Acronym / sponsor ID
- UCRI-1020
- Conditions
- Ulcerative Colitis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Glycominds, LLCIndustry (pharma, biotech, devices)
- Collaborators
- University of California, Davis, University of California, Irvine, University of Chicago, Weill Medical College of Cornell University, Crohn's and Colitis Foundation
- Study start
- 24 Aug 2021 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 21 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- Ulcerative colitis patients with Mayo Endoscopic Subscore of 2-3
- Start/switch anti -TNFa treatment
- Capable of at-home fCal testing
Key exclusion criteria (5 listed)
- Pregnant women
- anti -TNFa dose escalation/adjustment
- Inability to undergo endoscopic assessments due to Proctitis
- Diagnosed with infectious diseases
- Steroid refractory
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UCRIBiomarker panel and algorithm | Diagnostic test | – |
Primary outcome
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.
1 secondary outcome
fCal comparison analysis
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
- Background: PubMed 31628842de Bruyn M, Ringold R, Martens E, Ferrante M, Van Assche G, Opdenakker G, Dukler A, Vermeire S. The Ulcerative Colitis Response Index for Detection of Mucosal Healing in Patients Treated With Anti-tumour Necrosis Factor. J Crohns Colitis. 2020 Feb 10;14(2):176-184. doi: 10.1093/ecco-jcc/jjz125.
- Background: PubMed 21762664Koon HW, Shih DQ, Chen J, Bakirtzi K, Hing TC, Law I, Ho S, Ichikawa R, Zhao D, Xu H, Gallo R, Dempsey P, Cheng G, Targan SR, Pothoulakis C. Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology. 2011 Nov;141(5):1852-63.e1-3. doi: 10.1053/j.gastro.2011.06.079. Epub 2011 Jul 14.
- Individual participant dataSharing planned: No. MES, Treatment, MES, blinded patient characteristics and UCRI and fCal lab results will be shared with researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ulcerative Colitis, run by Glycominds, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Avinoam A Dukler, PhD (8057912094 ext. 1, ucri@glycominds.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
UCRI panel validation (time frame: 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04897282, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.