Clinical trial NCT02403622: Safety of FMT: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
Official title: Safety of Fecal Microbiota Transplantation: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Clostridium Difficile
Lead sponsor: Microbiome Health Research Institute
Sponsor class: OTHER
Collaborators: name: Brown University
name: Edward Hospital
name: Indiana University
name: Tufts Medical Center
First posted: 2015-03-31
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The overarching objective of this study is to address the knowledge gap regarding the short-term and long-term safety of fecal microbiota transplants (FMT). The design will be a prospective, open-label, multi-center longitudinal cohort study to assess the short- and long-term safety of FMT as well as the clinical resolution of diarrhea among 150 patients with 3 or more episodes of clostridium difficile infection (CDI defined as 3 unformed stools over 24 hours for 2 consecutive days and either a positive stool test for CDI or pseudomembranes on colonoscopy/sigmoidoscopy). Subjects will be adult outpatients referred to one of the study centers after at least three recurrent episodes of CDI and previous treatment with at least one 10-day course of oral vancomycin or fidaxomicin. After FMT by colonoscopy/sigmoidoscopy or enema, patients will be followed prospectively and monitored for clinical resolution and adverse events at: 3 days (telephone), 3 weeks (clinical assessment), 8 weeks (telephone), 6 months (telephone), and 12 months (telephone) after FMT. Subjects who recur will be offered a second FMT by colonoscopy with a different donor. Microbiome analysis will be conducted from stool samples at baseline and each of the 5 follow-up intervals.


Eligibility criteria: Inclusion Criteria:

* Adult (age 18-75 years old)
* Outpatient
* Third or further documented CDI episode and
* Unable to maintain CDI cure after standard therapy with oral vancomycin or fidaxomicin

  * Previous treatment with at least one course of tapered/pulse vancomycin or
  * Inability to taper or stop vancomycin or fidaxomicin without developing diarrhea requiring antibiotic therapy.
* Improvement of CDI symptoms on vancomycin or fidaxomicin

Exclusion Criteria:

* Unable to comply with study follow-up procedures at discretion of MD
* Unable to provide informed consent at discretion of MD
* Participating in another clinical trial
* Pregnant or nursing currently or planned pregnancy in next 1 year
* Evidence of toxic megacolon or gastrointestinal perforation
* Peripheral white blood cell count \>30 x 10\^9/L and/or temperature \>38 degrees Celsius
* Admission to an intensive care unit within prior 7 days for any reason
* Previously undergone FMT
* Severely immunocompromised patients

  * HIV infection (any CD4 count)
  * AIDS-defining diagnoses
  * Inherited/primary immune disorder
  * Immunosuppressant medications:
* Current or recent (\<3 months) treatment with anti-neoplastic agents
* Current or recent (\<3 months) treatment with calcineurin inhibitors (tacrolimus, cyclosporine)
* Current or recent (\<3 months) treatment with mycophenolate mofetil
* Current or recent (\<3 months) treatment with monoclonal antibodies to B and T-Cells, anti-TNF, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine)
* Neutropenia with absolute neutrophil count (ANC) \<0.5 x 10\^9/L
* Active gastroenteritis due to infectious cause other than CDI
* Short gut syndrome
* Colostomy
* Ascites
* End-stage liver disease
* Untreated, in-situ colorectal cancer
* Irritable bowel syndrome
* Inflammatory bowel disease including Crohn's disease and ulcerative colitis
* Microscopic colitis including collagenous colitis and lymphocytic colitis
* Severe food allergy (anaphylaxis) that cannot be confirmed as having been excluded from a donor's diet within the five days prior to donation
* Anorectal disorder/severe rectal sphincter tone abnormality or inability to retain enema material
* Unable or unwilling to tolerate colonoscopy/sigmoidoscopy, colonoscopy prep, or enema for any reason at discretion of MD
* Severe underlying disease that the patient is not expected to survive for the subsequent 12 months at the discretion of the MD.
* Any conditions for which, in opinion of MD, the treatment may pose a health risk

Primary outcomes:
measure: Short-term Safety of FMT as Measured by Absence or Presence of Related Serious Adverse Events
timeFrame: < 6 weeks post FMT
measure: Long-term Safety of FMT as Measured by Absence or Presence of Adverse Events
timeFrame: > 6 weeks to 1 year post FMT
Secondary outcomes:
Other outcomes:
Locations:
city: Naperville
country: United States
facility: Edward Hospital
state: Illinois
city: Indianapolis
country: United States
facility: IU University Hospital
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Providence
country: United States
facility: Brown University
state: Rhode Island
Study officials:
References: