Clinical trial NCT02797288: Immune Response to C.Difficile Infection
Official title: Clostridioides Difficile and Immune Responses in Acute CDI and Fecal Microbiota Transplant
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Clostridium Difficile
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2016-06-13
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Adaptive immune response
timeFrame: 0-60 days post enrollment
Secondary outcomes:
measure: Changes in gut health
timeFrame: 0-60 days post enrollment
measure: Gene expression of immune cells in colon
timeFrame: 0-60 days post enrollment
measure: Microbiome
timeFrame: 0-60 days post enrollment
measure: Immunohistochemistry
timeFrame: 0-60 days post enrollment
measure: Antibody response to C. difficile infection
timeFrame: 0-60 days post enrollment
measure: High dimensional flow-cytometry
timeFrame: 0-60 days post enrollment
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Virginia
name: William A. Petri, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: