Ignite Creation Date:
2025-12-25 @ 4:14 AM
Ignite Modification Date:
2025-12-26 @ 3:13 AM
Study NCT ID:
NCT07121920
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-08-14
First Post:
2025-08-12
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Ex-vivo Confocal Imaging and Proteomic Profiling to Determine Treatment Response in Children With IBD
Sponsor:
Cook Children's Health Care System
Organization:
Study Overview
Official Title:
A Prospective Study Evaluating Ex-vivo Confocal Imaging of Fluorescent Tagged Monoclonal Antibodies and Proteomic Profiles of Biopsied Tissue to Predict Therapeutic Response Among Children and Adolescents With Inflammatory Bowel Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study aims to test the overall hypothesis that the membrane tissue binding capacity of cytokines in the biopsied tissue of patients with Inflammatory Bowel Disease (IBD) is predictive of/strongly correlated to clinical response/outcomes observed.
The key questions under investigation are:
Aim 1: To assess the fluorescent signal intensity at baseline (control antibody with control biopsy and control antibody with IBD biopsy).
Aim 2: To characterize the cellular landscape by surveying surface markers using bar-coded antibodies and performing gene expression profiling on every cell within inflamed tissue of patients with IBD.
Aim 3: Develop algorithm using artificial intelligence to predict responders versus non-responders and to further subclassify IBD patients using phenotype data.
The key questions under investigation are:
Aim 1: To assess the fluorescent signal intensity at baseline (control antibody with control biopsy and control antibody with IBD biopsy).
Aim 2: To characterize the cellular landscape by surveying surface markers using bar-coded antibodies and performing gene expression profiling on every cell within inflamed tissue of patients with IBD.
Aim 3: Develop algorithm using artificial intelligence to predict responders versus non-responders and to further subclassify IBD patients using phenotype data.
Detailed Description:
It is estimated that approximately 5-10% of IBD patients develop the disease during childhood or adolescence. The disease onset peaks in adolescence, while 4% of children with IBD are less than 5 years of age and 18% below 10 years of age. IBD is characterized by a prolonged course of remission and relapse.
In patients with suspected IBD, endoscopy with biopsy is the gold standard method to diagnose and assess the degree and extent of inflammation. The impairment of intact intestinal epithelial barrier function is the hallmark of IBD, further involving a cascade of molecular and cellular alterations leading to delayed mucosal wound healing.
In the past decade, several studies examined the utility of probe-based confocal laser endomicroscopy (CLE) in several diseases, including IBD. The CLE is an emerging endoscopic technology developed to obtain high magnification and high-resolution images known as "optical" biopsies of the gastrointestinal mucosal histology in real-time at the cellular and sub-cellular levels.
The advantage of CLE during endoscopy is that normal tissue can be identified in real-time with high precision. A semi-quantitative test known as the Watson score was described by to describe structural and functional barrier defects in the terminal ileum in inflammatory bowel disease using CLE.
Although the use of biologics has revolutionized the management of IBD, it is estimated that approximately 10-40% of patients with IBD on biological agents like anti-TNF such as Infliximab (IFX) are primary non-responders, with an additional 13% per patient year experiencing a secondary loss of response. In children with moderate to severe Crohn's disease, it was estimated that only 67% would continue maintenance infliximab after three-years and approximately 50% of pediatric patients on IFX require dose intensification during maintenance therapy.
Limited studies have explored the binding of fluorescent labeled biologics ex-vivo using CLE in adults with little to no published literature in children. Studies in Europe have demonstrated that greater the binding of the biologic agent to the biopsied tissue pre-treatment, was associated with increased response to treatment, which was more pronounced in Ulcerative Colitis (AUROC 83%, PPV 89%, NPV 50%). A study abstract reported to have assessed the presence of fluorescein isothicyanate (FITC) labeled Vedolizumab (VDZ) prior to initiation of VDZ therapy in five patients with Crohn's Disease refractory to anti-TNF therapy. Among the 5, two of them showed α4β7 expressing mucosal cells and were found to have a good response to subsequent treatment with VDZ. However, further details of the study were not available. Similarly, a sustained improved response to anti-TNF treatment among patients with Crohn's Disease with high membrane-bound tumor necrosis factor (mTNF) intestinal immune cells using CLE evidenced by mucosal healing was observed on follow-up endoscopy compared to those who had low mTNF levels.
We sought to pursue the proposed study for the following reasons:
1. Unlike adults, IBD is more aggressive in children, for eg. impairs physical growth, impacting quality of life, in addition to the medication toxicities on top of the limited treatment options for IBD in pediatric patients.
2. The current approach in the management of IBD is treat to target, to achieve mucosal healing5 as subclinical inflammation could persist (as evidenced by endoscopy or histologically active disease) even though signs and symptoms have resolved. The above testing kit couples the use of CLE to determine treatment response, which aligns with the before-mentioned therapeutic goals in the management of IBD.
3. The cost of biologics are one of the major barriers to access of this promising treatment. At Cook Children's Health Care System, an average of 3-4 children/adolescents are diagnosed with Crohn's Disease or Ulcerative Colitis per week. Physicians can judiciously use biologics depending on treatment response assessed by the proposed testing kit, which will help alleviate the overall burden of cost incurred, to both the individual as well as to the healthcare system.
In patients with suspected IBD, endoscopy with biopsy is the gold standard method to diagnose and assess the degree and extent of inflammation. The impairment of intact intestinal epithelial barrier function is the hallmark of IBD, further involving a cascade of molecular and cellular alterations leading to delayed mucosal wound healing.
In the past decade, several studies examined the utility of probe-based confocal laser endomicroscopy (CLE) in several diseases, including IBD. The CLE is an emerging endoscopic technology developed to obtain high magnification and high-resolution images known as "optical" biopsies of the gastrointestinal mucosal histology in real-time at the cellular and sub-cellular levels.
The advantage of CLE during endoscopy is that normal tissue can be identified in real-time with high precision. A semi-quantitative test known as the Watson score was described by to describe structural and functional barrier defects in the terminal ileum in inflammatory bowel disease using CLE.
Although the use of biologics has revolutionized the management of IBD, it is estimated that approximately 10-40% of patients with IBD on biological agents like anti-TNF such as Infliximab (IFX) are primary non-responders, with an additional 13% per patient year experiencing a secondary loss of response. In children with moderate to severe Crohn's disease, it was estimated that only 67% would continue maintenance infliximab after three-years and approximately 50% of pediatric patients on IFX require dose intensification during maintenance therapy.
Limited studies have explored the binding of fluorescent labeled biologics ex-vivo using CLE in adults with little to no published literature in children. Studies in Europe have demonstrated that greater the binding of the biologic agent to the biopsied tissue pre-treatment, was associated with increased response to treatment, which was more pronounced in Ulcerative Colitis (AUROC 83%, PPV 89%, NPV 50%). A study abstract reported to have assessed the presence of fluorescein isothicyanate (FITC) labeled Vedolizumab (VDZ) prior to initiation of VDZ therapy in five patients with Crohn's Disease refractory to anti-TNF therapy. Among the 5, two of them showed α4β7 expressing mucosal cells and were found to have a good response to subsequent treatment with VDZ. However, further details of the study were not available. Similarly, a sustained improved response to anti-TNF treatment among patients with Crohn's Disease with high membrane-bound tumor necrosis factor (mTNF) intestinal immune cells using CLE evidenced by mucosal healing was observed on follow-up endoscopy compared to those who had low mTNF levels.
We sought to pursue the proposed study for the following reasons:
1. Unlike adults, IBD is more aggressive in children, for eg. impairs physical growth, impacting quality of life, in addition to the medication toxicities on top of the limited treatment options for IBD in pediatric patients.
2. The current approach in the management of IBD is treat to target, to achieve mucosal healing5 as subclinical inflammation could persist (as evidenced by endoscopy or histologically active disease) even though signs and symptoms have resolved. The above testing kit couples the use of CLE to determine treatment response, which aligns with the before-mentioned therapeutic goals in the management of IBD.
3. The cost of biologics are one of the major barriers to access of this promising treatment. At Cook Children's Health Care System, an average of 3-4 children/adolescents are diagnosed with Crohn's Disease or Ulcerative Colitis per week. Physicians can judiciously use biologics depending on treatment response assessed by the proposed testing kit, which will help alleviate the overall burden of cost incurred, to both the individual as well as to the healthcare system.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: