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

Microbiome Health Research Institute

Status and phase: Terminated; Phase 2

Conditions: Clostridium Difficile

Treatments: Drug: Fecal Microbiota Preparation

Study type: Interventional

Funder types: Other

Identifiers

NCT02403622

1410006671

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Intervention: Fecal Microbiota Preparation

Experimental group

Description:

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

Treatment:

Drug: Fecal Microbiota Preparation