Ex-vivo Confocal Imaging and Proteomic Profiling to Determine Treatment Response in Children With IBD

NCT ID: NCT07121920

Last Updated: 2025-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-01

Study Completion Date

2028-07-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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IBD (Inflammatory Bowel Disease) IBD IBD - Inflammatory Bowel Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Intervention

Pediatric patients with clinical signs and symptoms suggestive of IBD or with established diagnosis of IBD (newly diagnosed or on therapeutic management) who are scheduled to undergo Esophagogastroduodenoscopy (EGD) and/or Ileocolonoscopy (IC) with CLE as part of their clinical management

Group Type EXPERIMENTAL

Confocal Laser Endomicroscopy

Intervention Type DEVICE

Patients will undergo Esophagogastroduodenoscopy (EGD) and/or Ileocolonoscopy (IC) EGD with CLE as per standard of care. Each participant will have 3-4 mucosal biopsies taken from the terminal ileum, rectosigmoid and cecum, ideally from the most affected areas of accessible segment.

Ex vivo staining of biopsied tissue will be expanded to include FITC-labeled antibodies to cytokines IL12 and IL12/IL23 and to cytokine receptors IL12R and IL23R and possibly other cytokines, receptors and adhesion molecules. All biopsies tested for membrane bound antibodies will be done using CLE technology with artificial intelligence (AI). The cellular landscape will be characterized by surveying surface markers using bar-coded antibodies and performing gene expression profiling on every cell within inflamed tissue of patients with IBD.

We will develop algorithm using AI to predict responders versus non-responders and to further subclassify IBD patients using phenotype data.

Interventions

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Confocal Laser Endomicroscopy

Patients will undergo Esophagogastroduodenoscopy (EGD) and/or Ileocolonoscopy (IC) EGD with CLE as per standard of care. Each participant will have 3-4 mucosal biopsies taken from the terminal ileum, rectosigmoid and cecum, ideally from the most affected areas of accessible segment.

Ex vivo staining of biopsied tissue will be expanded to include FITC-labeled antibodies to cytokines IL12 and IL12/IL23 and to cytokine receptors IL12R and IL23R and possibly other cytokines, receptors and adhesion molecules. All biopsies tested for membrane bound antibodies will be done using CLE technology with artificial intelligence (AI). The cellular landscape will be characterized by surveying surface markers using bar-coded antibodies and performing gene expression profiling on every cell within inflamed tissue of patients with IBD.

We will develop algorithm using AI to predict responders versus non-responders and to further subclassify IBD patients using phenotype data.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

\- Patients must fall into one of the below categories: (i) with suspected and/or established diagnosis of IBD (ii) patients with IBD on treatment with biologics irrespective of treatment response (iii) patients who are diagnosed with IBD but treatment naïve to biologics. (iv) patients diagnosed with IBS and previous endoscopy results were negative for IBD who will serve as controls

Exclusion Criteria

* Those with previous allergy to fluorescein
* Pregnant and breastfeeding patients
Minimum Eligible Age

2 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cook Children's Health Care System

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clifton Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Cook Children's Health Care System

Locations

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University of Texas at Arlington

Arlington, Texas, United States

Site Status

Cook Children's Health Care System

Fort Worth, Texas, United States

Site Status

Countries

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United States

Central Contacts

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Sumith Roy, MBBS, MPH

Role: CONTACT

682-885-1790

Chief Research Officer

Role: CONTACT

Facility Contacts

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Jon Weidanz, PhD

Role: primary

817-272-6831

Sumith Roy, MBBS, MPH

Role: primary

682-885-1790

References

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Other Identifiers

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2024-083

Identifier Type: -

Identifier Source: org_study_id

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