International consensus on intestinal epithelial barrier assessment and therapeutic effects in inflammatory bowel diseases clinical trials.

Abstract

Restoration of intestinal barrier integrity and function in inflammatory bowel disease (IBD) has been associated not only with a reduced burden of persistent symptoms but also with improved long-term outcomes, prompting growing interest in intestinal barrier healing as a potential new therapeutic target. To date, no clinical trials have specifically evaluated therapies aimed at restoring intestinal barrier function in IBD, and there is currently no consensus on how such trials should be designed or how the intestinal barrier should be assessed. The aim of this initiative was to develop consensus recommendations on the optimal design of clinical trials and the selection of tools to evaluate therapies targeting the intestinal barrier in IBD. A panel of 12 international specialists with recognised expertise in the intestinal barrier and/or IBD clinical trials evaluated statements developed from a systematic literature review. Statements were discussed and anonymously voted on using a modified Delphi methodology. Consensus was predefined as at least 75% agreement among participants. The study was conducted and reported in accordance with the Conducting and REporting of DElphi Studies framework. Fourteen statements reached consensus and were approved. These statements addressed key aspects of clinical trial design, including the role of intestinal barrier assessment as an endpoint, timing of reassessment, protocol requirements and disease-specific considerations. Additional statements focused on the selection and standardisation of tools for intestinal barrier assessment, encompassing imaging-based techniques, functional permeability assays and endogenous biomarkers, as well as considerations for implementation and future research directions. This international consensus provides a structured framework to guide the design of future clinical trials evaluating efficacies of therapies in restoring intestinal barrier integrity and/or function in IBD.