safety of fmt: openbiome outcomes and longitudinal follow-up (stool) for recurrent clostridium difficile infection

Conditions: Clostridium Difficile

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