Immune Response to C.Difficile Infection

September 3, 2023 updated by: William Petri, MD, PhD, University of Virginia

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
360

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia Health System
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Acute CDI cohort: Hospitalized patients diagnosed with CDI

FMT cohort: Adult patients receiving fecal transplant for recurrent CDI identified from the University of Virginia complicated Clostridium difficile clinic

Past CDI Control cohort: Hospitalized patients with past CDI without recurrence

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Acute CDI cohort
Hospitalized patients diagnosed with Acute CDI
FMT cohort
Patients undergoing FMT for recurrent CDI
Past CDI Control Cohort
Hospitalized patients with past CDI diagnosis without recurrence

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adaptive immune response
Time Frame: 0-60 days post enrollment
Assessment of adaptive immunity including Th1, Th2 and TH17 immune response
0-60 days post enrollment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Changes in gut health
Time Frame: 0-60 days post enrollment
Association of biomarkers in stool and biopsy specimens with CDI outcome
0-60 days post enrollment
Gene expression of immune cells in colon
Time Frame: 0-60 days post enrollment
Profiling colonic gene expression and mucosal immune pathways in CDI
0-60 days post enrollment
Microbiome
Time Frame: 0-60 days post enrollment
Tissue 16s rDNA
0-60 days post enrollment
Immunohistochemistry
Time Frame: 0-60 days post enrollment
Changes in mucosal immunity following FMT
0-60 days post enrollment
Antibody response to C. difficile infection
Time Frame: 0-60 days post enrollment
IgG and IgA to C. difficile antigens in plasma and stool
0-60 days post enrollment
High dimensional flow-cytometry
Time Frame: 0-60 days post enrollment
Profiling of immune cells in blood and biopsy
0-60 days post enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Virginia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: William A. Petri, MD,PhD, University of Virginia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 22, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 27, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 7, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 13, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18782
  • R01AI124214-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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