Immune Response to C.Difficile Infection

NCT ID: NCT02797288

Last Updated: 2023-09-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 360 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-22
• Study Completion Date: 2025-01-01

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.

Conditions

Clostridium Difficile

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute CDI cohort

Hospitalized patients diagnosed with Acute CDI

No interventions assigned to this group

FMT cohort

Patients undergoing FMT for recurrent CDI

No interventions assigned to this group

Past CDI Control Cohort

Hospitalized patients with past CDI diagnosis without recurrence

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

William Petri, MD, PhD

Vice Chair, Department of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William A. Petri, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

William A. Petri, MD,PhD

Role: CONTACT

wap3g@virginia.edu

434-924-5621

Uma Nayak, PhD

Role: CONTACT

un8x@virginia.edu

434-982-3749

Facility Contacts

William A. Petri, MD,PhD

Role: primary

wap3g@virginia.edu

434-924-5621

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

R01AI124214-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18782

Identifier Type: -

Identifier Source: org_study_id