Safety of FMT: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection

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.

Inclusion Criteria:

- Adult (at least 18 years of age)

- 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 or travel to clinical site for follow-up visits 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 109/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 o Documented history (self- or physician identified) HIV infection with any cluster of differentiation 4 (CD4) count

- AIDS-defining diagnoses

- Inherited/primary immune disorder

- Immunosuppressant medications

- Neutropenia with absolute neutrophil count (ANC)
- 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