Immune Response to C.Difficile Infection

Clostridium Difficile Clinical Trial

Official title:

Clostridioides Difficile and Immune Responses in Acute CDI and Fecal Microbiota Transplant

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02797288
• Other study ID #: 18782
• Secondary ID: R01AI124214-01
• Status: Recruiting
• Start date: March 22, 2017
• Est. completion date: January 1, 2025

Study information

• Verified date: September 2023
• Source: University of Virginia
• Contact: William A. Petri, MD,PhD
• Phone: 434-924-5621
• Email: wap3g[@]virginia.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: January 1, 2025
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Clostridium Difficile

Locations

Country	Name	City	State
United States	University of Virginia Health System	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adaptive immune response	Assessment of adaptive immunity including Th1, Th2 and TH17 immune response	0-60 days post enrollment
Secondary	Changes in gut health	Association of biomarkers in stool and biopsy specimens with CDI outcome	0-60 days post enrollment
Secondary	Gene expression of immune cells in colon	Profiling colonic gene expression and mucosal immune pathways in CDI	0-60 days post enrollment
Secondary	Microbiome	Tissue 16s rDNA	0-60 days post enrollment
Secondary	Immunohistochemistry	Changes in mucosal immunity following FMT	0-60 days post enrollment
Secondary	Antibody response to C. difficile infection	IgG and IgA to C. difficile antigens in plasma and stool	0-60 days post enrollment
Secondary	High dimensional flow-cytometry	Profiling of immune cells in blood and biopsy	0-60 days post enrollment