Pathogenic Mechanisms in C Diff Infection and Colitis

Pathogenic Mechanisms in Clostridium Difficile Infection and Colitis

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.

Study Overview

• Status: Completed
• Conditions: Clostridium Difficile Infection

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 Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be selected from patients undergoing a routine screening colonoscopy at Beth Israel Deaconess Medical Center

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
All subjects

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 20, 2013
• First Submitted That Met QC Criteria: August 23, 2013
• First Posted (Estimate): August 28, 2013

Study Record Updates

• Last Update Posted (Actual): March 8, 2017
• Last Update Submitted That Met QC Criteria: March 6, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Clostridium difficile infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease Attributes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Colitis; Clostridium Infections
• Other Study ID Numbers: 2013P000174