Oral, Frozen Fecal Microbiota Capsules for Relapsing Clostridium difficile Infection
Methods: We performed an open-label, single-arm trial at the Infectious Diseases Clinic of Massachusetts General Hospital. Healthy volunteers were screened and FMT capsules were generated and stored in -800 C. Twenty patients (median age 64.5y; range 11-89) with relapsing or refractory CDI as defined by consensus guidelines were included. Patients received 15 capsules on two consecutive days and were followed for symptom resolution and development of adverse events for up to 6 months. The primary endpoints were safety, assessed by adverse events grade 2 or above, and resolution of diarrhea with no relapse at 8 weeks. Secondary endpoints included improvement in subjective well-being per standardized questionnaires and daily number of bowel movements.
Results: No serious adverse events attributed to FMT were observed. Resolution of diarrhea was achieved in 14 (70%) after a single FMT with capsules. All six relapsing patients were retreated, with 5 obtaining cure, resulting in an overall 95% cure rate (19/20). These results are similar to those observed in our previous study, in which the liquid inoculum was administered via colonoscopy or nasogastric tube (18/20; p=1.00). Daily number of bowel movements changed from a median (IQR) of 5 (3-6) the day prior to administration to 2 (1-3) at day 3 (p=0.03) and 1 (1-2) at 8 weeks (p<0.001). Self-ranked health scores improved significantly from a median (IQR) of 5 (5-7) for overall health and 4.5 (3-7) for gastrointestinal specific health the day prior to FMT; to 8 (7-9) post-administration for both groups (p=0.001).
Conclusion: FMT using oral administration of a frozen encapsulated inoculum from unrelated donors appears to be safe and effective in treating relapsing CDI. Larger studies are needed to confirm these results, as well as long-term safety and effectiveness.
C. Pindar, None
J. Sauk, None
E. Hohmann, Seres Health : Investigator, Research support