Immune Response to C.Difficile Infection

Recruiting

• Conditions: Clostridium Difficile

• Registration Number: NCT02797288
• Lead Sponsor: University of Virginia

Brief Summary

The protocol aims to address the basic mechanisms of Clostridium difficile pathogenesis by identifying how a Th 17 response impacts severity of C. difficile infection and how Type II immunity protects the gut from Clostridium difficile toxin-induced damage. This could lead to new and effective approaches to the treatment or prevention of Clostridium difficile colitis that act downstream of fecal microbiota transplants (FMT) or next generation probiotics. Successful fecal microbial transplantation will restore protective immunity to recurrent C.difficile infection.

Detailed Description

The study includes one cohort of hospitalized patients with acute CDI who may require diagnostic colonoscopy, a second cohort of outpatients with recurrent CDI scheduled for FMT and a third cohort of inpatients with past history of CDI without recurrence.

Blood samples and discarded stool samples for research will be obtained from adult hospitalized patients. Biopsies and brushing samples for research will be obtained from patients requiring diagnostic colonoscopies for clinical care. Follow-up will include phone contact at 60-90 days to determine relapse or mortality in acute CDI patients.

Blood and colonic biopsies and brushing samples will be obtained from patients undergoing FMT for recurrent CDI and again after 60 days from convalescent patients.

Blood and biopsies taken for research purposes at each colonoscopy will be analyzed for: cytokines and chemokines, gene expression analysis, immunohistochemistry and high dimensional flow-cytometry.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-05-27
• Study First Submitted QC: 2016-06-07
• Study First Posted: 2016-06-13
• Study Start: 2017-03-22
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-03
• Last Update Posted: 2023-09-06
• Primary Completion: 2024-10-31
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

-Acute CDI cohort

• Acute CDI diagnosis including PCR positive fecal samples
• Optional diagnostic colonoscopy for clinical care

FMT cohort

• At least one relapse or recurrence of C. difficile infection
• Eligible for fecal microbiota transplant (FMT)

Past CDI cohort

• Past CDI diagnosis and current PCR negative fecal samples
• Optional diagnostic colonoscopy for clinical care

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Exclusion Criteria

Acute CDI cohort:

• Unwilling to have research biopsies and brushings at time of diagnostic colonoscopy; Unwilling to provide blood and stool samples (discarded stool from UVA lab) for research
• Unwilling to participate in follow-up phone call at 60-90 days
• Concurrent participation in another clinical trial. This exclusion does not apply to participation in IRB-HSR #200046 and non-interventional research studies. Concurrent participation in non-interventional research studies is allowed.
• Clinical contraindication to colonoscopy or conscious sedation
• Pregnancy
• Inability to give informed consent unless a legally authorized representative (LAR) is available
• Incarceration
• HIV infection

FMT cohort:

• Unwilling to have research biopsies and brushings and stool samples at time of colonoscopy with FMT for clinical care and research sigmoidoscopy at Day 60
• Unwilling to provide blood samples for research
• Concurrent participation in another clinical trial This exclusion does not apply to participation in non-interventional research studies. Concurrent participation in non-interventional research studies is allowed.
• Clinical contraindication to sigmoidoscopy or conscious sedation
• Pregnancy
• Inability to give informed consent
• Incarceration
• HIV infection
• Neutropenia (<1000 PMNs/µl blood)

Past CDI Control cohort:

• Unwilling to have research biopsies and brushings at time of diagnostic colonoscopy; Unwilling to provide blood and stool samples (discarded stool from UVA lab) for research
• Concurrent participation in another clinical trial. This exclusion does not apply to participation in IRB-HSR #200046 and non-interventional research studies. Concurrent participation in non-interventional research studies is allowed.
• Clinical contraindication to colonoscopy or conscious sedation
• Pregnancy
• Inability to give informed consent unless a legally authorized representative (LAR) is available
• Incarceration
• HIV infection

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Adaptive immune response	0-60 days post enrollment	Assessment of adaptive immunity including Th1, Th2 and TH17 immune response

Secondary Outcome Measures

Name	Time	Method
Microbiome	0-60 days post enrollment	Tissue 16s rDNA
Immunohistochemistry	0-60 days post enrollment	Changes in mucosal immunity following FMT
Changes in gut health	0-60 days post enrollment	Association of biomarkers in stool and biopsy specimens with CDI outcome
Gene expression of immune cells in colon	0-60 days post enrollment	Profiling colonic gene expression and mucosal immune pathways in CDI
Antibody response to C. difficile infection	0-60 days post enrollment	IgG and IgA to C. difficile antigens in plasma and stool
High dimensional flow-cytometry	0-60 days post enrollment	Profiling of immune cells in blood and biopsy

Trial Locations

Locations (1)

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States