Warren, Cirle A.Shin, Jae HyunBansal, Ekta N.Costa, Deiziane V. D. S.Wang, Xin QunWu, MartinSwann, Jonathan R.Behm, Brian W.Targonski, Paul V.Archbald-Pannone, Laurie2024-06-102024-06-102023-07-192044-6055bmjopen-2023-075721 (PII)https://hdl.handle.net/10919/119373Introduction: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. Methods and analysis: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. Ethics and dissemination: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. Trial registration number NCT04305769.7 page(s)application/pdfenCreative Commons Attribution-NonCommercial 4.0 Internationalgastrointestinal infectionsinfectious diseasesgastroenterologyrandomized controlled trialclinical trialsHumansClostridium InfectionsNeoplasm Recurrence, LocalInflammationTreatment OutcomeDouble-Blind MethodDietary SupplementsAdolescentAdultRandomized Controlled Trials as TopicClinical Trials, Phase II as TopicClostridioides difficileArticle - Refereedhttps://doi.org/10.1136/bmjopen-2023-075721137Bansal, Ekta [0000-0003-1989-9493]374741812044-6055