A Framework for Clinical Trials of Neurobiological Interventions That Target the Gut-Brain Axis in Inflammatory Bowel Disease

Abstract

A growing body of evidence from preclinical, translational, and clinical studies supports a bidirectional relationship within the gut-brain axis that contributes to neurobiological symptoms including anxiety, depression, fatigue, stress, and sleep disturbance. These symptoms have a significant impact on health-related quality of life and functional ability in individuals with inflammatory bowel disease. Clinical studies that generate high-quality evidence on pharmacological and nonpharmacological (eg, psychosocial, behavioral) interventions are needed to ultimately improve access to safe and effective therapies that have a meaningful impact on patients and to guide medical and regulatory decisions. This review outlines a framework for designing and conducting randomized controlled trials for interventions that target neurobiological symptoms in patients with inflammatory bowel disease based on the most recent guidance published within the past 5 years from policy makers, clinicians specialized in inflammatory bowel disease, patient-reported outcomes methodologists, health economists, patient advocates, industry representatives, ethicists, and clinical trial experts.

Keywords: anxiety; clinical trials; depression; endpoints; fatigue; neurobiological symptoms; patient-reported outcomes; psychological symptoms; randomized control trial; sleep; stress.