Fecal Transplant for Relapsing C. Difficile Infection
|Clostridium Difficile||Biological: Fecal Microbiota Transplantation Biological: Sham Fecal Microbiota Transplantation||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Fecal Microbiota Transplantation for Relapsing Clostridium Difficile Infection|
- Clinical Cure [ Time Frame: 8 weeks ]Resolution of diarrhea (i.e., fewer than three unformed stools for two consecutive days), with maintenance of resolution for the duration of the 8 week follow-up period and no further requirements for anti-infective therapy for C. difficile infection). Subjects who meet this definition will be considered cured regardless of results of follow-up stool testing for C. difficile.
- Clinical Failure [ Time Frame: 8 weeks ]Persistence or development of diarrhea and the need for additional anti-infective therapy for C. difficile infection with or without positive stool testing (PCR) for C. difficile. Upon clinical failure, subject's treatment will be unblinded and those who received sham Fecal Microbiotia Transplantation (FMT) may chose to receive open label FMT using donor stool. Subjects, who received true FMT and develop clinical failure, may chose to undergo a second FMT using an alternate donor.
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 6 months ]Subjects will be followed closely for significant adverse events and adverse events during the 8 week follow up period post-FMT and the development of new medical conditions/diagnoses or changes in medical conditions/medications will be determined at 6 month follow up contact. Adverse events will be tabulated by study arm.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||September 2015|
|Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Active Comparator: 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 fecal Microbiota Transplant (FMT) with a 300 mL donor fecal suspension delivered via colonoscopy.
Biological: Fecal Microbiota Transplantation
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: Sham Fecal Microbiota Transplantation
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.
Biological: 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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01703494
|United States, New York|
|Montefiore Medical Center|
|The Bronx, New York, United States, 10467|
|United States, Rhode Island|
|The Miriam Hospital|
|Providence, Rhode Island, United States, 02906|
|Principal Investigator:||Colleen R Kelly, MD||Lifespan; The Miriam Hospital.|
|Principal Investigator:||Lawrence J Brandt, MD||Montefiore Medical Center|