Fecal Transplant for Relapsing C. Difficile Infection
Fecal Transplant for Relapsing C. Difficile Infection
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.
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.
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.