Biomarker Discovery, Validation, and Multi-Omics Profiling for Disease Activity Assessment, Treatment Monitoring, and Risk Stratification in Inflammatory Bowel Disease: A Multicenter Prospective Biospecimen-Based Observational Cohort Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 6,000
- Locations
- 2
- Primary Endpoint
- Diagnostic Performance of Candidate Biomarkers or Combined Biomarker Models for Endoscopic Disease Activity
Study Overview
Brief Summary
The goal of this observational study is to establish a multicenter prospective clinical and biospecimen platform for biomarker discovery and validation in inflammatory bowel disease, including Crohn's disease and ulcerative colitis.
Researchers want to learn whether candidate biomarkers or combined biomarker models can help assess intestinal inflammation, monitor response to routine clinical treatment, predict treatment outcomes, and identify participants who may be at higher risk of disease progression.
The study may enroll participants with inflammatory bowel disease, unaffected first-degree relatives of participants with inflammatory bowel disease, unrelated healthy controls, and non-IBD disease controls when appropriate. Clinical information and biological samples, including blood, stool, and intestinal tissue, may be collected. Biomarkers measured in blood, stool, intestinal tissue, genetic data, immune profiles, microbiome data, and other multi-omics data may be evaluated.
The main questions this study aims to answer are:
Can candidate biomarkers or combined biomarker models identify endoscopic disease activity when compared with endoscopic assessment?
Can these biomarkers monitor or predict clinical response, clinical remission, endoscopic response, endoscopic remission, imaging response, or biomarker response during routine clinical care?
Can these biomarkers help predict treatment failure, disease progression, hospitalization, surgery, treatment escalation, or complex Crohn's disease phenotypes?
Participants will not be assigned to any treatment by the study. All treatments and clinical management decisions will be chosen by treating physicians as part of routine medical care.
Detailed Description
This is a multicenter prospective observational cohort study designed to establish a clinical data and biospecimen-based platform for biomarker discovery, validation, and multi-omics research in inflammatory bowel disease. The study will enroll participants with inflammatory bowel disease, including Crohn's disease, ulcerative colitis, or IBD-unclassified when applicable, as well as unaffected first-degree relatives, unrelated healthy controls, and non-IBD disease controls when appropriate.
The study is not designed to assign or test any study-directed treatment. All medical treatments, including biologic therapies, targeted small-molecule therapies, nutritional therapy, endoscopy, imaging, surgery, and other clinical management decisions, will be determined by treating physicians according to routine clinical practice. The study will observe participants during routine care and collect standardized clinical data, biospecimens, endoscopic findings, histologic findings, laboratory results, imaging findings, treatment exposure information, and follow-up outcomes.
The overall purpose of this study is to evaluate whether candidate biomarkers or combined biomarker models can be used to assess disease activity, identify endoscopic and histologic inflammation, monitor response to routine clinical treatment, predict treatment outcomes, and support risk stratification for disease progression. Endoscopic assessment will serve as the primary reference standard for evaluating biomarker performance for objective intestinal inflammation.
The study is intended to function as an open biomarker discovery and validation platform. It will evaluate both pre-specified biomarkers and additional candidate biomarkers identified through genetic, pharmacogenetic, immune, microbiome, transcriptomic, proteomic, metabolomic, single-cell, tissue-based, spatial, or other multi-omics analyses. Pre-specified biomarker domains may include blood-based biomarkers, stool-based biomarkers, tissue-based biomarkers, genetic markers, immune-related markers, microbiome-derived markers, and multi-omics-derived candidate biomarkers. Examples may include leucine-rich alpha-2 glycoprotein, fecal calprotectin, C-reactive protein, oncostatin M, TL1A/TNFSF15-related markers, TNFSF15 genotype, selected HLA or other pharmacogenetic markers when available, and additional biomarkers selected from exploratory omics analyses.
The primary analysis will evaluate the diagnostic performance of candidate biomarkers or combined biomarker models for endoscopic disease activity. Reference measures may include SES-CD, standardized small-bowel endoscopic assessments, capsule endoscopy scores, Mayo endoscopic score, UCEIS, or other accepted endoscopic assessments when applicable. Performance measures may include area under the receiver operating characteristic curve, sensitivity, specificity, predictive values, and biomarker cut-off values. Cut-off values may be explored in discovery datasets and evaluated in internal and external validation cohorts.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 14 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Eligibility Criteria:
- •Inclusion Criteria:
- •General inclusion criteria for all participants:
- •Age 14 years or older.
- •Able to provide written informed consent; for minors, consent from a legal guardian and assent from the participant will be obtained according to local ethics requirements.
- •Willing to provide clinical information and/or biospecimens, which may include blood, stool, intestinal tissue, or other available biological samples.
- •Able to participate in study-related data and sample collection according to the study protocol.
- •Participants with inflammatory bowel disease:
- •Diagnosed with inflammatory bowel disease, including Crohn's disease, ulcerative colitis, or IBD-unclassified when applicable, according to accepted national or international diagnostic criteria.
- •May be newly diagnosed, previously diagnosed, under routine follow-up, or receiving routine clinical treatment.
- •Clinical data, treatment exposure information, laboratory results, endoscopic findings, histologic findings, imaging findings, biospecimens, and follow-up outcomes may be available or collected.
- •Unaffected first-degree relatives of participants with inflammatory bowel disease:
- •Biological first-degree relatives of participants with inflammatory bowel disease, including parents, siblings, or offspring.
- •No prior diagnosis of inflammatory bowel disease at enrollment.
- •Willing to provide clinical information and/or biospecimens for family-based genetic, environmental, immune, microbiome, and multi-omics analyses.
- •Unrelated healthy controls:
- •Individuals without a diagnosis of inflammatory bowel disease.
- •No first-degree biological relationship to enrolled participants with inflammatory bowel disease.
- •No known active gastrointestinal inflammatory disease at enrollment.
- •Non-IBD disease controls:
- •Individuals with gastrointestinal symptoms or other non-IBD conditions who undergo clinical evaluation but are not diagnosed with inflammatory bowel disease.
- •Clinical information and/or biospecimens may be collected as disease controls when appropriate.
Exclusion Criteria
- •Refusal or inability to provide informed consent or required assent when applicable.
- •Active severe infection or chronic infectious disease that may substantially affect biomarker interpretation, including active tuberculosis, active hepatitis B or C, HIV infection, or other clinically significant active infection.
- •Pregnancy or lactation at the time of enrollment.
- •Severe mental illness, cognitive impairment, or other condition that prevents cooperation with study procedures.
- •Known primary extraintestinal autoimmune disease or systemic inflammatory disease that is considered the main disease and may substantially confound biomarker interpretation.
- •Current or recent participation in another interventional clinical trial that may substantially affect the study biomarkers or outcome assessments, as judged by the investigator.
- •History of malignant tumor or other severe comorbidity that may substantially affect study participation or biomarker interpretation, as judged by the investigator.
- •Inadequate biospecimen quality, missing key clinical information, or inability to complete essential study assessments for the relevant analysis.
Outcomes
Primary Outcomes
Diagnostic Performance of Candidate Biomarkers or Combined Biomarker Models for Endoscopic Disease Activity
Time Frame: At paired biospecimen and endoscopy assessments, with biospecimen collection within 30 days before or after endoscopy; assessed from enrollment through 52 weeks per participant
Diagnostic performance of pre-specified and newly identified candidate biomarkers or combined biomarker models for identifying endoscopic disease activity in inflammatory bowel disease. Endoscopic assessments will serve as the primary reference standard. Reference measures may include SES-CD, standardized small-bowel endoscopic assessments, capsule endoscopy scores, Mayo endoscopic score, UCEIS, or other accepted endoscopic assessments when applicable. Performance measures will include AUC, sensitivity, specificity, positive predictive value, negative predictive value, and biomarker cut-off values. Cut-off values will be explored in discovery datasets and evaluated in internal and external validation cohorts.
Predictive Performance of Candidate Biomarkers or Combined Biomarker Models for Treatment Response
Time Frame: From treatment baseline to induction assessment at approximately 12 to 16 weeks; maintenance assessment up to 52 weeks when available
Predictive performance of baseline candidate biomarkers, longitudinal biomarker changes, or combined biomarker models for response to routine clinical treatment will be evaluated. Treatment response outcomes may include clinical response, clinical remission, endoscopic response, endoscopic remission, inflammatory marker response, imaging response, treatment escalation, treatment failure, hospitalization, surgery, or relapse when available. Treatments are not assigned by the study and are recorded only as routine-care clinical exposures.
Secondary Outcomes
- Diagnostic Performance of Candidate Biomarkers or Combined Biomarker Models for Histologic Disease Activity and Remission(At paired biospecimen and histologic assessments, with biospecimen collection within 30 days before or after tissue sampling; assessed from enrollment through 52 weeks per participant when available)
- Concordance and Predictive Performance of Candidate Biomarkers or Combined Models for Clinical Remission Rate(At treatment baseline and routine-care follow-up assessments, including induction assessment at approximately 12 to 16 weeks and maintenance assessment up to 52 weeks per participant when available)
- Concordance and Predictive Performance of Candidate Biomarkers or Combined Models for Clinical Response Rate(At treatment baseline and routine-care follow-up assessments, including induction assessment at approximately 12 to 16 weeks and maintenance assessment up to 52 weeks per participant when available)
- Concordance Between Candidate Biomarkers or Combined Models and Fecal Calprotectin for Intestinal Inflammatory Activity(At paired biospecimen and fecal calprotectin assessments at baseline, induction assessment at approximately 12 to 16 weeks, and maintenance assessment up to 52 weeks per participant when available)
- Concordance Between Candidate Biomarkers or Combined Models and C-Reactive Protein for Systemic Inflammatory Activity(At paired biospecimen and C-reactive protein assessments at baseline, induction assessment at approximately 12 to 16 weeks, and maintenance assessment up to 52 weeks per participant when available)
- Predictive Performance of Candidate Biomarkers or Combined Models for Cross-Sectional Imaging-Defined Radiologic Response Rate(From treatment baseline MRE or CTE to follow-up MRE or CTE at approximately 12 to 16 weeks and up to 52 weeks per participant when available)
- Predictive Performance of Candidate Biomarkers or Combined Models for Cross-Sectional Imaging-Defined Radiologic Remission Rate(From treatment baseline MRE or CTE to follow-up MRE or CTE at approximately 12 to 16 weeks and up to 52 weeks per participant when available)
- Predictive Performance of Candidate Biomarkers or Combined Models for Intestinal Ultrasound-Defined Response Rate(From treatment baseline intestinal ultrasound to follow-up intestinal ultrasound at approximately 12 to 16 weeks and up to 52 weeks per participant when available)
- Predictive Performance of Candidate Biomarkers or Combined Models for Intestinal Ultrasound-Defined Remission or Transmural Healing Rate(From treatment baseline intestinal ultrasound to follow-up intestinal ultrasound at approximately 12 to 16 weeks and up to 52 weeks per participant when available)
- Predictive Performance of Candidate Biomarkers or Combined Models for Disease Progression and Poor Outcomes(From enrollment to the end of available follow-up, up to 5 years per participant when available)
Investigators
Wei Wang
Attending Physician
Sixth Affiliated Hospital, Sun Yat-sen University