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.
Brief Title
Safety of FMT: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
Completion Date
Completion Date Type
Actual
Conditions
Clostridium Difficile
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
75 Years
Minimum Age
18 Years
NCT Id
NCT02403622
Org Class
Other
Org Full Name
Microbiome Health Research Institute
Org Study Id
1410006671
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Safety of Fecal Microbiota Transplantation: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
Primary Outcomes
Outcome Description
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
Outcome Measure
Short-term Safety of FMT as Measured by Absence or Presence of Related Serious Adverse Events
Outcome Time Frame
< 6 weeks post FMT
Outcome Description
Determine the long-term safety of FMT for the prevention of further CDI recurrence
Outcome Measure
Long-term Safety of FMT as Measured by Absence or Presence of Adverse Events
Outcome Time Frame
> 6 weeks to 1 year post FMT
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
75
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Olga Aroniadis
Investigator Email
oaroniad@montefiore.org
Investigator Phone