Pathogenic Mechanisms in C Diff Infection and Colitis

Completed

• Conditions: Clostridium Difficile Infection

• Registration Number: NCT01930032
• Lead Sponsor: Beth Israel Deaconess Medical Center

Brief Summary

The purpose of this study is to learn more about infection by Clostridium difficile (also known as C. difficile). C. difficile is a common bacterium (a germ that may cause disease) that can live in the human gut. Some people have it without having any symptoms. In other people it can cause illness ranging from mild diarrhea to severe colitis (infection of the colon).

C. difficile makes toxins that damage the cells that line the colon. The study doctors want to find out how these toxins cause damage to the cells in the colon.

Detailed Description

The purpose of this study is to examine pathogenic mechanisms of Clostridium difficile toxin-mediated intestinal injury and inflammation. Two primary mechanisms will be examined.

* To examine the hypothesis is that microRNA expression profiles are dysregulated by Clostridium difficile toxin exposure and that dysregulation of miRNA expression plays a role in the pathogenesis of C. difficile associated diseases.

* To examine the hypothesis is that the TLR9 receptor mediates key inflammatory events in response to Clostridium difficile toxin exposure.

Study Timeline

• Study Start: 2013-08
• Study First Submitted: 2013-08-20
• Study First Submitted QC: 2013-08-23
• Study First Posted: 2013-08-28
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-06
• Last Update Posted: 2017-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Age greater than 18 yrs and less than 75 years
• Undergoing a clinically indicated colonoscopy

Exclusion Criteria

• Known, active or recurrent colonic disease including: Clostridium difficile infection, inflammatory bowel disease, microscopic colitis, colon resection for any reason, ischemic colitis, recurrent diverticulitis, colon cancer. Note: Diverticulosis without recurrent diverticulitis, colonic adenomatous or hyperplastic polyps or colonic arteriovenous malformations will not constitute an exclusion
• Diarrhea (an average of more than 3 bowel movements per day at baseline)
• Constipation (an average of fewer than 2 bowel movements per week at baseline).
• Use of systemic steroid or systemic immunosuppressive medication
• Severe renal impairment
• Relative contraindication to colon biopsy including a bleeding diathesis or anti-coagulant use. Note: nonsteroidal antiinflammatory drug or asprin use will not constitute a contra-indication.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Binding of Toxin A (and B) to TLR9 on the human colorectal epithelial cell surface	24 hours	As assessed by confocal fluorescence microscopy

Secondary Outcome Measures

Name	Time	Method
Binding of Toxin A (and B) to TLR9 on the human colorectal epithelial cell surface	6 hours	As assessed by confocal fluorescence microscopy
effects of a TLR9 antagonist (ODN-TTAGGG) on toxin binding	0 hours	The change of mean toxin fluorescence on colonocytes will be measured by confocal microscopy using quantitative image analysis software.
Effects of a TLR9 antagonist (ODN-TTAGGG) on toxin binding	24 hours	The change of mean toxin fluorescence on colonocytes will be measured by confocal microscopy using quantitative image analysis software.

Trial Locations

Locations (1)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States