Ignite Creation Date:
2025-12-25 @ 2:44 AM
Ignite Modification Date:
2026-01-06 @ 9:32 AM
Study NCT ID:
NCT02729233
Status:
WITHDRAWN
Last Update Posted:
2018-01-08
First Post:
2016-03-31
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Predicting Clinical Response to Golimumab With Mucosal Barrier Dysfunction
Sponsor:
University of Arkansas
Organization:
Study Overview
Official Title:
Predicting Clinical Response to Golimumab With Mucosal Barrier Dysfunction
Status:
WITHDRAWN
Status Verified Date:
2018-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding withdrawn
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD). UC is an ongoing disease of the colon or large intestine. Studies have shown that leakiness of the gut plays a major role in the development of UC. Leakiness of the gut is a condition that is a result of damage to the intestinal lining, making it less able to protect its internal environment as well as to filter needed nutrients and other substances. Some bacteria, toxins, and waste not normally absorbed may get into the blood stream.
Golimumab is an FDA approved medication used for the treatment of moderate to severe ulcerative colitis. The investigators have evidence to suggest that measuring the leakiness of the gut using a tool called a confocal laser endomicroscope may be able to predict how well a patient's body will respond to treatment of UC with golimumab. Confocal laser endomicroscopy (CLE) is an FDA approved technique that can look at the cells of a patient's gut during colonoscopy to assess the leakiness of gut.
The objective of this study is to determine how the leakiness of the gut in patients with UC can predict response to golimumab therapy.
Golimumab is an FDA approved medication used for the treatment of moderate to severe ulcerative colitis. The investigators have evidence to suggest that measuring the leakiness of the gut using a tool called a confocal laser endomicroscope may be able to predict how well a patient's body will respond to treatment of UC with golimumab. Confocal laser endomicroscopy (CLE) is an FDA approved technique that can look at the cells of a patient's gut during colonoscopy to assess the leakiness of gut.
The objective of this study is to determine how the leakiness of the gut in patients with UC can predict response to golimumab therapy.
Detailed Description:
The objective of this pilot study is to determine the predictive value of mucosal barrier dysfunction for a therapeutic response to golimumab in UC patients. This objective is based on the investigator's hypothesis that barrier dysfunction is a potent predictor of response to anti-tumor necrosis factor (TNF) therapy. This hypothesis is based on the following observations: (1) IBD patients with higher gap densities have higher mucosal pro-inflammatory cytokine levels; (2) the highest rates of response to biologic therapy for Ulcerative colitis are seen in post-operative patients, with over 90% endoscopic remission rate at one year; and (3) prominent barrier dysfunction is observed at the anastomotic site in animal models of ileal resection. Therefore, the investigators hypothesize that barrier dysfunction is a potent predictor of therapeutic response to golimumab in UC patients.
In 30 UC patients who will be started on golimumab for treatment of UC (moderate to severe flare, steroid dependence, or failure of other therapies), epithelial barrier function will be characterized using probe-based CLE (pCLE). Six mucosal biopsies will be collected from each site (terminal ileum and rectum) for histologic verification of pCLE findings at baseline, and again at month 12 for a total of 12 research samples per colonoscopy, or 24 research biopsy samples during the course of the study. The study subjects will be followed for a total of 1 year after initial colonoscopy with pCLE. The primary study end-point is clinical response at 3 months following initiation of golimumab.
Secondary study endpoints are: (1) The rate of clinical remission at 3 months following initiation of golimumab. (2) The rate of clinical remission at 12 months following initiation of golimumab. (3) Endoscopic and histological evidence of mucosal healing at one-year follow-up colonoscopy.
Clinical Response \& Remission definitions are: (1) Clinical Remission: partial Mayo score of 2 points, without any sub-score \>1. (2) Clinical Response: reduction of partial Mayo UC score by ≥ 30% and ≥ 2 points, with a rectal bleeding sub-score of ≤ 1 or a decrease in the bleeding sub-score of ≥ 1.
Endoscopic and histologic mucosal healing definitions: (1) Endoscopic: Mayo endoscopic score of 0 or 1. (2) Histologic: Riley's histological score ≤ 6.
The investigators proposal is based on clinical, translational and basic evidence of barrier dysfunction in the pathogenesis of UC. With the development of a robust prediction model for therapeutic response, UC patients can be treated more effectively with golimumab. Using a stratified approach, higher therapeutic response rate may eventually yield a new "intelligent step-up" treatment strategy in this personalized medicine era.
In 30 UC patients who will be started on golimumab for treatment of UC (moderate to severe flare, steroid dependence, or failure of other therapies), epithelial barrier function will be characterized using probe-based CLE (pCLE). Six mucosal biopsies will be collected from each site (terminal ileum and rectum) for histologic verification of pCLE findings at baseline, and again at month 12 for a total of 12 research samples per colonoscopy, or 24 research biopsy samples during the course of the study. The study subjects will be followed for a total of 1 year after initial colonoscopy with pCLE. The primary study end-point is clinical response at 3 months following initiation of golimumab.
Secondary study endpoints are: (1) The rate of clinical remission at 3 months following initiation of golimumab. (2) The rate of clinical remission at 12 months following initiation of golimumab. (3) Endoscopic and histological evidence of mucosal healing at one-year follow-up colonoscopy.
Clinical Response \& Remission definitions are: (1) Clinical Remission: partial Mayo score of 2 points, without any sub-score \>1. (2) Clinical Response: reduction of partial Mayo UC score by ≥ 30% and ≥ 2 points, with a rectal bleeding sub-score of ≤ 1 or a decrease in the bleeding sub-score of ≥ 1.
Endoscopic and histologic mucosal healing definitions: (1) Endoscopic: Mayo endoscopic score of 0 or 1. (2) Histologic: Riley's histological score ≤ 6.
The investigators proposal is based on clinical, translational and basic evidence of barrier dysfunction in the pathogenesis of UC. With the development of a robust prediction model for therapeutic response, UC patients can be treated more effectively with golimumab. Using a stratified approach, higher therapeutic response rate may eventually yield a new "intelligent step-up" treatment strategy in this personalized medicine era.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: