Lyophilized Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection
Lyophilized Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection
The primary goal is to study participants with recurrent C. difficile infection (CDI) treated
 with lyophilized fecal microbiota transplantation (FMT). The safety, clinical response and
 relapse rate in patients will be assessed.
Recurrence of CDI following a course of standard antibiotic therapy is high, especially in
 the elderly patients over 65 years of age, in hospitalized and in the immunocompromised
 patients. As CDI is characterized by intestinal dysbiosis. Fecal Microbiology Transplantation
 (FMT) has been investigated as alternative treatment for CDI and has been determined to be
 effective and safe. One of the major challenges of offering FMT is the availability of
 suitable donors. A donor may no longer be able to continue to donate for a number of reasons
 and this may lead to temporary interruption of FMT in centers which offer the program. In
 order to continue to offer FMT whenever needed, we will investigate the efficacy of
 lyophilized FMT. The lyophilization (freeze-drying) process works by dehydrating a frozen
 donor stool sample to complete dryness, using controlled temperature and pressure gradients.
 This lyophilized process results in a powdered form of the sample. Studies have shown that
 lyophilized donor stool samples have similar microbial compositions as the same fresh
 sample.The technique of freeze drying has been used for decades for the industrial storage of
 microbes and has been used. Preliminary study of lyophilized stool for FMT has been performed
 in dogs. Preliminary efficacy data in dogs with inflammatory bowel disease suggest equal
 efficacy as compared to fresh stool, although controlled study has yet to be performed.
 Should the lyophilized FMT (L-FMT) demonstrate to be equally or more effective than frozen
 FMT, there would be significant advantages. As with frozen FMT, lyophilized FMT will allow
 patients to receive FMT immediately as it can take up to two weeks for a donor's screening
 laboratory testing results to be available. Lyophilized FMT will also be more cost effective
 as less number of donors will need to be screened given the prolonged shelf life of
 lyophilized FMT which can be kept at above the freezing temperature. 9 This will also allow
 wider distribution and accessibility especially to the regions with limited capacity to
 manufacture FMT.
Inclusion Criteria:

 -  Age ≥ 12 years or older.

 -  Able to provide informed consent.

 -  Willing and able to comply with all the required study procedures.

 -  A positive stool test for C. difficile toxin/gene using either PCR or enzyme
 immunoassay within 3 months of recruitment unless patient taking treatment
 specifically for CDI for more than 3 months.

 -  History of at least ≥ 2 recurrent CDI where recurrence is deﬁned as return of diarrhea
 consistent with CDI within 8 weeks following CDI symptom resolution for at least 24
 hours after a minimum of 10-day course of standard antibiotic therapy for each episode
 and/or ongoing symptoms consistent with CDI* (defined below) despite at least 7 days
 of treatment using oral vancomycin at a minimum dose of 250 mg four times daily.

 -  Symptoms of CDI include: diarrhea deﬁned as: 3 or more unformed bowel movements
 in 24 hours for a minimum of 2 days with no other causes for diarrhea

 Exclusion Criteria:

 -  Planned or actively taking another investigational product

 -  CDI symptom-free for 3 or more weeks following completion of CDI treatment

 -  Patients with neutropenia with absolute neutrophil count <0.5 x 109/L

 -  Evidence of toxic megacolon or gastrointestinal perforation on abdominal x-ray

 -  Active gastroenteritis due to Salmonella, Shigella, E. coli 0157H7, Yersinia or
 Campylobacter.

 -  Presence of colostomy

 -  Unable to tolerate FMT or enema for any reason.

 -  Requiring systemic antibiotic therapy for more than 7 days.

 -  Actively taking Saccharomyces boulardii or other probiotic; yogurt is allowed

 -  Severe underlying disease such that the patient is not expected to survive for at
 least 30 days.