Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection

At the time of writing, 202 patients had been treated with FMT capsules at Massachusetts General Hospital. The outcomes of 180 patients who had completed an 8 week follow-up assessment (with 154 completing follow-up/reaching 6 months) are reported herein. Patients over the age of 7 years, with three or more mild-to-moderate episodes of CDI or two episodes requiring hospitalization, were offered capsule FMT. Absolute exclusions were neutropenia (absolute neutrophil count??500) and prednisone??40 mg/day; other immuno-suppressed patients were considered with agreement of referring physicians. The study was reviewed and approved by the Partners Human Research Committee Institutional Review Board and submitted to the Food and Drugs Administration (IND 16011, sponsor E. Hohmann MD). Recipients or parents provided written consent, which discussed the risks, benefits, and investigational nature of the procedure. Children provided assent. Donor screening, preparation of the frozen capsules, FMT procedures, and patient follow-up were unchanged from the previous report [9]. Briefly, donors were healthy adults with a normal body mass index, passed the American Association of Blood Banks donor questionnaire, and underwent physical examination and extensive laboratory testing for general health and infectious diseases as described [9].

Donated fecal matter was blenderized, sieved, centrifuged, and suspended in concentrated form in sterile saline with 10 % glycerol. The suspension was double-encapsulated in hypromellose capsules (Capsugel, Cambridge, MA) and stored at –80 °C for up to 6 months pending use. Processing was done entirely under ambient air. FMT recipients discontinued any anti-CDI treatment for 24–48 hours prior to FMT, and were given 15 capsules on each of two consecutive days with water or apple sauce. The 30 capsules contained sieved, concentrated material derived from a mean of 48 g of fecal matter. Recipients were nil per os 4 hours before and 1 hour after dosing. Those with worsening diarrheal symptoms at least 72 hours after the second dosing day had fecal samples retested for C. difficile. If they had diarrhea and still tested positive, they were retreated with 4–14 days of standard antibiotic therapy for CDI and were offered another FMT. Patients were followed on a standardized schedule by phone (3–5 days, 10–14 days, 2 months, and 6 months after FMT) with structured questionnaires recording stool frequency, general and gastrointestinal well-being, and mild, moderate, or severe adverse events (grades 1, 2, or 3 based upon CTCAE V.4.0). The primary endpoint was defined as clinical resolution/no relapse of diarrhea whilst off antibiotics for CDI at 8 weeks after last capsule ingestion and safety, defined as any FMT-related adverse events grade 2 or above. Resolution of diarrhea was defined as three or fewer bowel movements per 24 hours. For brevity going forward we have defined this resolution as a “cure” though we appreciate “resolution of symptoms/no relapse” may be preferred. Fecal microbiome analyses were beyond the scope of this treatment study.