This trial is active, not recruiting.

Condition clostridium difficile
Treatments fecal microbiota transplantation, sham fecal microbiota transplantation
Phase phase 2
Sponsor Colleen Kelly
Start date October 2012
End date May 2015
Trial size 53 participants
Trial identifier NCT01703494, 1R21DK093839-01A1


There has been an alarming increase in the incidence and severity of Clostridium difficile infection (CDI) in North America over the past decade. Relapsing infection is a common problem in patients treated for CDI, often requiring prolonged and expensive courses of oral vancomycin with limited alternative treatment options. This study will determine if fecal microbiota transplantation, which involves administering fecal flora from a healthy stool donor to a patient with relapsing CDI, is an effective and safe treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
(Active Comparator)
After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive fecal Microbiota Transplant (FMT) with a 300 mL donor fecal suspension delivered via colonoscopy.
fecal microbiota transplantation FMT
Fecal microbiota transplantation (FMT) involves administering fecal material from a healthy individual (donor) to a sick patient (with relapsing C. difficile infection) to restore missing components of normal intestinal flora. After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive fecal microbiota transplantation (FMT) with a 300 mL donor fecal suspension delivered via colonoscopy.
(Sham Comparator)
After completing at least a 10 day course of vancomycin for treatment of the most recent acute severe C. difficile infection, subjects will receive a 300 mL infusion of a sham (autotransfusion) fecal solution at colonoscopy.
sham fecal microbiota transplantation
After completing at least a 10 day course of vancomycin for treatment of the most recent acute C. difficile infection, subjects will receive a sham fecal microbiota transplantation (FMT) with a 300 mL sham fecal suspension delivered via colonoscopy. This sham solution will be a reinfusion of the subject's own stool.

Primary Outcomes

Clinical Cure
time frame: 8 weeks

Secondary Outcomes

Clinical Failure
time frame: 8 weeks

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

Inclusion Criteria: 1. Adult outpatients (age ≥18 and <75) referred to one of the study centers after suffering a third (or further) documented episode CDI and 2. who have failed to maintain CDI cure after standard therapy with oral vancomycin. - Previous treatment with at least one course of tapered/pulse dose vancomycin as per SHEA-IDSA C difficile treatment guidelines or -Inability to taper or stop vancomycin without developing diarrhea requiring anti-infective therapy. - Exclusion Criteria: - Patients who are aged 75 years or greater. - Patients who are pregnant - Patients who are nursing - Patients who are incarcerated - Patients with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving their own informed consent - Patients who are immunocompromised specifically: - HIV infection (any CD4 count) - AIDS-defining diagnosis or CD4<200/mm3 - Inherited/primary immune disorders - Immunodeficient or Immunosuppressed due to medical condition/medication: - Current or recent (<3 most) treatment with anti-neoplastic agent - Current or recent (<3 mos) treatment with any immunosuppressant medications (including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil). Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll. - Patients with a history of severe (anaphylactic) food allergy - Patients who have previously undergone FMT - Patients who are unwilling or unable to undergo colonoscopy - Patients with untreated, in-situ colorectal cancer - Patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn‟s disease or microscopic colitis) or irritable bowel syndrome - Unable to comply with protocol requirements - Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V - Patients with acute illness or fever on the day of planned FMT will be excluded (not undergo randomization or treatment with FMT) with the option of including that subject at a future date.

Additional Information

Official title Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection
Principal investigator Colleen R Kelly, MD
Description Clostridium difficile is an increasingly common infection. The number of hospital discharges for which C. difficile was listed as the first diagnosis more than doubled between 2000 and 2003. In addition to occurring more frequently, there is an epidemic of serious cases which are more refractory to therapy and which have high rates of colectomy and death. Most commonly, C. difficile infection (CDI) is associated with use of antimicrobial agents that are thought to alter the normal bacterial flora of the gastrointestinal tract so as to permit colonization and/or proliferation and toxin elaboration by C. difficile. Though the precise mechanisms by which this occurs are still incompletely understood, depletion of physiologic microflora, in particular Bacteroides species may play an important role. Most patients with CDI respond to a course of oral metronidazole or vancomycin, however, up to 20% of patients relapse after initial treatment. Current guidelines recommend a tapering course of vancomycin after a second recurrence, however up to 60% of patients still do not respond to this treatment strategy or develop further recurrence after the vancomycin is stopped. Use of antimicrobials to treat CDI may predispose these patients to further relapses through the maintenance of disturbed intestinal flora and may contribute to the emerging problem of drug resistance. "Fecal Microbiota Transplantation" (FMT) is a novel treatment approach which involves administration of feces from a healthy (donor) individual into a patient with relapsing CDI to promote recolonization with missing components of normal intestinal flora. Numerous case reports and retrospective case series have suggested benefit of FMT in patients with severe or recurrent CDI with cure rates as high as 100% and a mean cure rate of 89% for the nearly 300 cases reported in the world literature. Although efficacy has been documented in these case reports, to date there has not been a published prospective clinical trial of FMT for CDI. The proposed study would be the first randomized, double-blind, placebo (sham) controlled clinical trial to determine whether FMT delivered at colonoscopy is effective at preventing further relapse in patients who have suffered from at least a 3rd recurrence of CDI despite receiving standard treatment. The investigators hypothesize that FMT is superior to placebo in preventing relapse after treatment of CDI with vancomycin. As a result of this study, the investigators will have preliminary efficacy data for this novel treatment approach for recurrent CDI. The investigators will be better prepared to test the efficacy of FMT in future multicenter clinical trials. This research will advance clinical care, potentially impacting the protocol for treatment of relapsing C. difficile infection worldwide. This proposal includes collaboration with an investigator capable of performing microbiome analyses on specimens collected as part of the trial and will further understanding of the intestinal microflora in health and disease.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by The Miriam Hospital.