Alanyl-glutamine supplementation of standard treatment for C. difficile infection

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PROJECT SUMMARY C. difficile is the leading cause of antibiotic-associated diarrhea and nosocomial infection. Antibiotic treatment is the standard approach in managing C. difficile infection (CDI) and is associated with high recurrence rates of up to 65% depending on the number of previous disease. Alanyl-glutamine prevents C. difficile toxin-induced impairment of cell migration and proliferation in intestinal cell lines, secretion and histopathology in animal ileal tissues, and increased apoptosis in vitro and in vivo. We have shown that in the mouse model of CDI, alanyl- glutamine supplementation significantly reduced diarrhea, weight loss, histopathology, relapse and deaths in vancomycin-treated mice. A small pilot study in human suggests that alanyl-glutamine may prevent recurrent disease up to 6 months after CDI treatment. We hypothesize that supplementation with alanyl-glutamine will improve outcomes of treatment of CDI in humans. To prove this hypothesis, we plan to conduct a randomized, double-blinded, placebo-controlled trial. The specific aims of this project are 3-fold. First, we shall determine the optimal dose of oral alanyl-glutamine on preventing recurrence and deaths in patients treated with standard anti-C.difficile agents. Secondly, we shall demonstrate the safety of oral alanyl- glutamine supplementation. And thirdly, we shall test the effect of alanyl-glutamine on intestinal inflammation, barrier function and gut flora in patients undergoing standard treatment for CDI. This research proposal will allow for a rigorous, safe and productive performance of the clinical trial to prove the benefit of alanyl-glutamine in human disease, potentially introducing a novel approach to treatment of CDI.