Alanyl-glutamine supplementation for Clostridioides difficile infection treatment (ACT): a double-blind randomised controlled trial study protocol
Jonathan R Swann,
Paul V Targonski,
Cirle A Warren,
Jae Hyun Shin,
Ekta N Bansal,
Deiziane V D S Costa,
Xin Qun Wang,
Martin Wu,
Brian W Behm,
Laurie Archbald-Pannone
Affiliations
Jonathan R Swann
School of Human Development and Health, University of Southampton Faculty of Medicine, Southampton, UK
Paul V Targonski
Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
Cirle A Warren
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Jae Hyun Shin
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Ekta N Bansal
Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, Virginia, USA
Deiziane V D S Costa
Department of Medicine, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Xin Qun Wang
Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
Martin Wu
Department of Biology, University of Virginia College and Graduate School of Arts and Sciences, Charlottesville, VA, USA
Brian W Behm
Department of Medicine, Division of Gastroenterology and Hepatology, University of Virginia School of Medicine, Charlottesville, VA, USA
Laurie Archbald-Pannone
Department of Medicine, Division of General, Geriatric, Palliative & Hospital Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
Introduction 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.
