Early FMT for C.Difficile
Condition: Clostridium Difficile
MeSH terms: Clostridium Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Clostridium difficile infection (CDI) has increased worldwide in both frequency and severity.
      It is the leading cause of hospital acquired infection in developed countries and has been
      associated with at least 14,000 deaths per year in the United States. With 3 million cases/
      year, the annual cost for treating the infection is exceeding 3 billion dollars. It can also
      have a profound negative impact on quality of life.

      The investigators believe that patients who are at high risk of relapse after a first CDI
      episode would benefit from early fecal microbial transplant (FMT). The proposed study will
      produce preliminary data regarding safety and efficacy and potential for cost effectiveness
      for the use of early fecal transplant in those patients with their first episode of
      non-refractory CDI who are predicted to have a high rate of recurrence based on previously
      published risk factors. The investigators will be better prepared to test the efficacy of
      this approach in a future multicenter clinical trial in a randomized controlled fashion.

      The purpose of this study is to compare the effectiveness and safety of early fecal
      transplant using donor stool from a healthy person in a group of patients who are diagnosed
      with their first episode of Clostridium difficile infection and are predicted to have a high
      chance of the infection returning against a similar group of patients who receive current
      standard of care for treatment of C.difficile.

      The investigators hypothesize:

        -  that clinical remission rates at 12 weeks as noted by absence of clinical symptoms
           and/or negative C.difficile stool polymerase chain reaction (PCR) will be greater in the
           experimental arm compared to the control arm

        -  that patients in the experimental group will have a low microbial diversity prior to FMT
           but will exhibit a high microbial diversity after the FMT that resembles the respective
           donor

        -  that the microbial diversity will be diminished in both groups at the time of
           enrollment, but the experimental group will exhibit a higher microbial diversity
           compared to the control population at 12 weeks

        -  that patients in both groups will exhibit poor quality of life at the time of
           enrollment, however, the experimental group will demonstrate higher quality of life
           compared to the control group at follow up after completion of treatment

        -  that costs incurred by the experimental group will be less than the control group
    

Detailed description: 
      Treatment of CDI remains challenging, especially in those with recurrent disease. Failures
      rates of 20-30% with initial treatment have been reported, and up to 65% fail after a third
      course of antibiotics. In addition, costs of treatment, which can be upward of $3000 for a 10
      day course of a single antibiotic, may leave many patients and their families financially
      overburdened. Use of FMT has shown to be effective with cure rates above 80%, safe even in
      immunocompromised patients, and cost effective in those with recurrent (3 or more) episodes
      of C.difficile. Emory University and Emory Clinic have performed over 100 FMT's since July
      2012 for treatment of recurrent or refractory CDI and has had similar cure rates.

      Current treatment approaches for CDI limit the use of fecal transplant to those who have had
      more than 2 recurrences with at least one failure of a 6-8 week taper with vancomycin or at
      least 2 episodes of severe CDI resulting in hospitalization or refractory CDI defined as
      moderate CDI not responding to standard therapy for at least one week (5). However, the
      investigators feel that by attempting to perform FMT early after a first episode in those at
      high risk of recurrence, decreased recurrence rates, improved quality of life, and lower
      health care costs will be seen.

      Patients who participate will be randomized to one of two groups - one group who receives a
      fecal transplant and another group who will not receive a fecal transplant. A fecal
      transplant using a sigmoidoscopy will occur after the subjects in the fecal transplant arm
      complete the course of antibiotics for treatment of the C.difficile infection. Healthy stool
      from a donor will be infused into the colon to help replenish good bacteria that patients
      with C.difficile infection often do not have. The group that does not undergo FMT will take
      antibiotics and probiotic therapy for management of CDI as part of standard of care.
    

Intervention name(s): Fecal microbiota transplant (FMT); flexible sigmoidoscopy
Intervention type(s): Procedure; Device
Intervention description(s): 250 mL of donor stool will be infused into the colon by flexible sigmoidoscopy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: fecal microbiota transplant; probiotic