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

Study Overview
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Brief Summary
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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.

Official Title
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Safety of Fecal Microbiota Transplantation: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Drug: Fecal Microbiota Preparation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention: Fecal Microbiota Preparation<br>Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor | Drug: Fecal Microbiota Preparation<br>* Frozen processed human fecal material for treating recurrent Clostridium difficile infections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term Safety of FMT as Measured by Absence or Presence of Related Serious Adverse Events | Determine the short-term safety of FMT for the prevention of further CDI recurrence. Short-term safety was measured by absence or presence of related serious adverse events | < 6 weeks post FMT | 
| Long-term Safety of FMT as Measured by Absence or Presence of Adverse Events | Determine the long-term safety of FMT for the prevention of further CDI recurrence | > 6 weeks to 1 year post FMT |