Predicting Clinical Response to Golimumab With Mucosal Barrier Dysfunction

NCT02729233 | Withdrawn

• 1 other identifier: 205241
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ulcerative Colitis

Keywords

mucosal barrier function

Outcome Measures

Primary Outcomes (1)

• Rate of improvement in mucosal barrier function as measured by pCLE

  up to 12 months

Study Arms (1)

patients receiving biopsies

OTHER

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 confocal laser endomicroscopy (pCLE).

Other: patients receiving biopsies

Interventions

patients receiving biopsies OTHER

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.

patients receiving biopsies

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ulcerative colitis based on standard clinical, radiological, endoscopic and histological criteria with moderate-to-severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore of 2 or more.
• Age 18-75 years
• Patients about to be started on golimumab therapy because of moderate to severe flare, steroid dependence, or failure of other therapies.
• Inadequate response to or failure to tolerate 1 or more of the following conventional therapies:
• Oral 5-aminosalicylates (5-ASAs)
• Oral corticosteroids
• Immunosuppressives (azathioprine (AZA) or 6-mercaptopurine) OR
• Corticosteroid-dependent (i. e., could not taper corticosteroids without recurrence of UC symptoms) AND
• No previous exposure to biological therapy (TNF naïve)
• Patients concurrently treated with oral 5-aminosalicylates or corticosteroids must have maintained stable dose for ≥ 2 weeks before baseline.
• Patients concurrently treated with AZA and/or 6-mercaptopurine must have maintained stable dose for ≥ 4 weeks before baseline.
• Tuberculosis (TB) related screening criteria:
• No history of latent or active tuberculosis (TB) prior to screening. An exception is made for subjects who have a history of latent TB and are currently receiving treatment for latent TB, will initiate treatment for latent TB prior to first administration of golimumab, or have documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of golimumab.
• No signs or symptoms suggestive of active TB upon medical history and/or physical examination.
• No recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to the first administration of study agent.

You may not qualify if:

• Pregnancy/nursing.
• Known allergies to IV contrast or shellfish.
• Impaired renal function (serum creatinine over 1.5 mg/dL).
• Uncontrolled or severe asthma.
• Active infection.
• Active or previously identified latent tuberculosis.
• History of systemic lupus.
• Current or history of demyelinating neurological disease.
• Current or history of congestive heart failure.
• History of or at imminent risk for colectomy.
• Gastrointestinal surgery ≤ 2 months prior to screening for study entry.
• Colitis limited to 20 cm. of the colon.
• History of colonic mucosal dysplasia or adenomatous colonic polyps that were not removed.
• Screening stool sample positive for enteric pathogens or Clostridium difficile toxin.
• Previous use of the following medications:

Sponsors & Collaborators

• University of Arkansas: lead
• Janssen Scientific Affairs, LLC: collaborator

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Julia J Liu, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: April 6, 2016
• Study Start: January 1, 2017
• Primary Completion: January 27, 2017
• Study Completion: January 27, 2017
• Last Updated: January 8, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share