Safety of FMT: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
Condition: Clostridium Difficile
MeSH terms: Clostridium Infections
Intervention: Fecal Microbiota Preparation
Intervention description: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

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