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Active C. Difficile Colitis clinical trials

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NCT ID: NCT01868373 Enrolling by invitation - Clinical trials for Active C. Difficile Colitis

Defined Fecal Microbiota Transplantation for Clostridium Difficile Diarrhea

Start date: February 28, 2013
Phase: Phase 1
Study type: Interventional

To confirm and extend the work of Trede and Rask-Madsen (Lancet 1989;1:1156-1160) that administration of a defined fecal microbiota will lead to rapid and sustained resolution of C. difficile associated chronic relapsing diarrhea. The current rationale behind FMT for CDI is that introduction of microbes from a healthy donor allows restoration of a normal microbial community in the diseased host with consequent suppression of C. difficile colonization and disease pathogenesis. The first modern use of FMT was reported in a 1958 case series of 4 patients with pseudomembranous enterocolitis. The first case of confirmed CDI treated with FMT was reported in 1983; treatment was curative. Until 1989, retention enemas were the most common technique for FMT. Alternative methods for delivering FMT have included fecal infusion via duodenal tube (1991), rectal tube (1994), and colonoscopy (1998). FMT for recurrent CDI has been used successfully whether administered by nasogastric tube, rectal administration by colonoscopy, rectal tube including self-administration at home by enema. FMT has proven to be remarkably effective and remarkably safe without any significant problems (see below and attached reviews and meta-analyses). Increasing, interest is emerging regarding the changes in the intestinal microbiota associated with CDI. In 2008 Chang et al. constructed small (< 200 sequences per subject) 16S rRNA gene libraries from the stools of 4 patients with first-time CDI and 3 patients with recurrent CDI. Based on 16S rRNA gene classification, they found that the fecal microbiomes of patients with an initial episode of CDI were similar at the phylum level to healthy subjects (i.e., the majority of sequences belonged to dominant fecal phyla Bacteroidetes and Firmicutes), while a major reduction or loss of Bacteroidetes was observed in patients with recurrent CDI. The loss of the Bacteroidetes was accompanied by the expansion of other phyla, including Proteobacteria and Verrucomicrobia, which are normally minor constituents of the fecal microbiota. Khoruts et al. (2010) compared the microbiota of a patient with recurrent CDI before and after FMT by using terminal-restriction fragment length polymorphism and clone-based 16S rRNA gene sequencing. Before transplantation, the patient's microbiota were deficient in members of Bacteroides and instead were composed of atypical fecal genera such as Veillonella, Clostridium, Lactobacillus, Streptococcus, and unclassified bacteria similar to Erysipelothrix. Two weeks after infusion of donor fecal suspension, the bacterial composition of her feces approached normal and was dominated by Bacteroides sp. strains. In 1989, Tvede and Rask-Madsen used a combination of nine normal fecal organisms to treat 6 patients with chronic relapsing C. difficile diarrhea. These investigators cultivated 10 strains of bacteria, including Enterococcus (Streptococcus) faecalis (1108-2), Clostridium innocuum (A27-24), Clostridium ramosum (A3I-3), Bacteroides ovatus (A40-4), Bacteroides vulgatus (A33-14), Bacteroides thetaiotaomicron (A33-12), Escherichia coli (1109), E. coli (1108-1), Clostridium bifermentans (A27-6), and Blautia producta (Peptostreptococcus productus) (1108-2) in broth for 48 h to a concentration of approximately 10 to the 9th power bacteria/mL. Two mL from each bacterial culture were admixed with 180 mL saline that had been pretreated in an anaerobic chamber for 24 h; the bacterial suspension was then instilled rectally. This procedure was followed promptly by a decline of C. difficile to undetectable levels by culture and the loss of detectable toxin from the stools. Normal bowel function was restored within 24 hours, and abdominal symptoms disappeared. Stool cultures and toxin assays for C. difficile remained negative during a year of follow-up. It is especially important to note that feces from none of the 6 patients contained Bacteroides sp.