Background: The period prior to the diagnosis of inflammatory bowel disease (IBD), defined as the preclinical phase, has emerged as a potential target for disease modification strategies. Despite the relevance of an early diagnosis to the prognosis of the disease, only a limited number of patients are diagnosed during this window of opportunity.
Objectives: To determine the risk of developing symptoms after an incidental diagnosis of IBD and to describe the clinical, genetic, and immunological characteristics of IBD during its preclinical phase.
Design: This study protocol describes a prospective, multicenter cohort study in which incidental (i.e., asymptomatic) IBD within the colorectal cancer screening program will be characterized from a clinical and multi-omic perspective and compared with symptomatic patients and healthy non-IBD controls.
Methods: Samples from blood, urine, stool, and intestinal endoscopic biopsies will be obtained at baseline. A second sample set will be obtained after 52 weeks from those who remain asymptomatic; samples will also be obtained in those with new-onset symptoms. Medical treatment will be prescribed in all patients following current guidelines. Follow-up visits will be performed every 6 months for 10 years, and all new-onset symptoms, changes in disease behavior, extraintestinal manifestations, IBD-related medical therapies, or surgeries will be recorded. Two control cohorts will be included: one including recently diagnosed symptomatic IBD patients (<3 months), and another with healthy non-IBD controls after a normal ileocolonoscopy, in whom samples will be obtained at baseline. Samples from patients and controls will undergo genetic, proteomic, transcriptomic, single-cell RNA sequencing, metabolomic, and microbiome analyses, and integration of data between the different omic perspectives will also be performed. The study has been approved by the Basque Country Ethics Committee (PI2021116).
Conclusion: EARLY will generate a unique dataset addressing a previously unexplored area of IBD, with the final aim of describing the prognosis of patients from its earlier phases on the disease and integrating clinical and omic data into useful tools for the long-term prediction of disease outcomes.
Trial registration: NCT05698745.
Keywords: Crohn’s disease; biomarkers; early; natural history; prediction; ulcerative colitis.
Study protocol of a study on the natural history, immunological and genetic characteristics of the early phases of inflammatory bowel disease (EARLY) This study focuses on inflammatory bowel disease (IBD) and aims to explore the period before symptoms appear, known as the preclinical phase. Detecting IBD early could improve patient outcomes, but currently, few patients are diagnosed during this phase. The study seeks to determine the risk of developing symptoms after an incidental IBD diagnosis (discovered without symptoms) and to describe the clinical, genetic, and immune characteristics of IBD in this early stage. It involves a prospective, multicenter approach, examining patients who are incidentally diagnosed with IBD during colorectal cancer screening. These patients will be compared to those with symptomatic IBD and healthy individuals without IBD. Researchers will collect samples of blood, urine, stool, and intestinal tissue from participants at the start of the study and again after one year if they remain symptom-free. Additional samples will be taken if symptoms develop. Participants will receive standard medical treatment and have follow-ups every six months for ten years. The study will track new symptoms, changes in disease behavior, extraintestinal symptoms, treatments, and surgeries. Two control groups will be included: one with recently diagnosed symptomatic IBD patients and another with healthy individuals who had normal colonoscopy results. The samples will undergo extensive genetic and molecular analyses to integrate data from different perspectives. The EARLY study will generate a valuable dataset on the early stages of IBD, aiming to understand the prognosis from its earliest phases and to combine clinical and molecular data to predict long-term outcomes.
© The Author(s), 2025.