Combination Therapy of Resilience Intervention with Biologics in Crohn's Disease (CATHARSIS): Study protocol for a randomized controlled trial

Background: Remission rates in Crohn's disease (CD) with standard therapies have plateaued in recent decades. There is a need to investigate more innovative strategies to raise the “therapeutic ceiling”. Combining orthogonal treatments that target differing pathways of disease pathogenesis may maximize synergistic therapeutic efficacy. In particular, the addition of interventions that target the gut-brain axis warrant investigation. Our overarching goal is to demonstrate the value of a new “combination therapy” that addresses psychological and physical health simultaneously, targeting the gut-brain axis, to improve CD outcomes. We will test the efficacy of combining brain-gut behavior therapy with biologic treatment in a randomized, controlled clinical trial, following behavioral clinical trial guidelines for gastroenterology. Methods: We will recruit 170 adults with CD aged between 18 and 80 years starting an anti-tumor necrosis factor or anti-interleukin-23 medication. Participants will be randomized in a 1:1 ratio to receive a program of either brain-gut behavioral therapy (intervention group) or emotional support (time and attention control group). Both programs consist of seven sessions within a 12-week period. Patient-reported outcomes including well-being and disease activity will be measured at weeks 0, 12, 24, 36, and 52, with the primary outcomes reflected at week 24. Outcomes will be evaluated for group X time interactions. Conclusions: This trial will be the first of its kind to rigorously evaluate the efficacy of a treatment approach that combines brain-gut behavioral therapy and biologics for people with CD.