Clinical Core

Overview

The overarching goal of the CSIBD Clinical Core is to provide an infrastructure that facilitates the translation of basic research findings into the clinic. The Core is led by Ramnik Xavier, MD, PhD (Director), Andrew Chan, MD, MPH (Co-director), and Ashwin Ananthakrishnan, MD, MPH (Technical director). All three of these individuals are gastroenterologists with particular expertise and interest in translational medicine relating to IBD. Key components of this Core are the PRISM (Prospective Registry in IBD Study at MGH) and GIDER (GI Disease and Endoscopy Registry) registries, which together include more than 4,400 enrolled IBD patients and healthy controlled individuals.

Objectives

1. Build a biorepository of patients with Crohn's disease and ulcerative colitis with accurate phenotyping of disease as well as sampling of blood, stool, urine and tissue in various disease states (active/inactive disease) and related to various therapeutic and environmental perturbations
2. Develop and expand longitudinal cohorts of health and disease anchored around disease diagnosis, prediction of relapse, and response to specific therapies in patients with IBD
3. Define the phenotypic implications of genetic loci and microbial perturbation with regard to clinical manifestations, response to therapy, and to examine the interaction with the environment, making these results available in an IBD knowledgebase that includes both ‘omics data and patient metadata
4. Facilitate education and training in research by providing consultations regarding study design, methods and analysis as well as attracting new investigators to the field through these services
5. Translate laboratory and clinical research findings into interventions that improve diagnosis, develop biomarkers for disease monitoring and prognostication, and optimize treatment algorithms

Clinical Database and Patient Identification

The Clinical Core maintains an active database encompassing patients with IBD seen at Massachusetts General Hospital. Because the entire GI staff at Mass General participates in a common group practice organization and all are committed to the success of this project, it has been possible to capture nearly all relevant patients for this base.

Retrospective review of hospital admissions suggests that < 5% of patients with an identified diagnosis of IBD are cared for without the participation of members of the GI group. Furthermore, as most of the small numbers missed by these criteria are admitted for surgical procedures, this group is identified through the activity of the tissue collection mechanisms of this core.

Demographic data are available on all patients seen through the GI group and hospital at large. The database includes demographics and salient disease features, including symptoms, duration, medications, location of disease (means of documentation), extraintestinal manifestations, endoscopy, surgery, pathology, family history and hospitalizations.

Patients are also asked to indicate if they would be willing to participate in CSIBD-related research activities through the PRISM or GIDER cohorts. CSIBD investigators with IRB-approved projects have access to this database to identify patients needed for study. An additional responsibility of this core is the recruitment of patients for specific study needs through notification of all Mass General GI Unit practitioners.

Services

Services include expansion of the patient registries and initiation of longitudinal IBD patient cohorts, generation of a single-cell atlas of ulcerative colitis, refined biospecimen collection algorithms, development of standard operating procedures (SOP) for processing of tissues, facilitation of regulatory paperwork and institutional review board (IRB) approval of protocols, integration of genetic and microbiome data with clinical data, expansion of depth of phenotyping and assessment of exposures, and streamlined user access to clinical and biospecimen data.

• Consultation, training, and education
  • Consulting in research methods and analysis
  • Weekly multidisciplinary clinical conferences focusing on patient care, which are used to foster research collaborations between scientists and clinicians
  • Several courses offered every month through the Mass General Division of Clinical Research in clinical investigation, clinical trial design, translational research and database management
  • Mass General Advanced IBD Fellowship, which supports one or two advanced fellows every year
  • In collaboration with the Crohn's and Colitis Foundation, 2-3 junior trainees (Visiting Fellows) from other institutions are hosted at the MGH Crohn's and Colitis Center. In addition to providing clinical training, such trainees are exposed to clinical and translational investigation in IBD through involvement with the PRISM registry
  • Physician-scientist gastroenterology fellow trainees supported by grant T32 DK007191 pursue research mentored by core investigators; these projects often employ the clinical data and biospecimens collected within our prospective registries
  • Resident trainees from the Department of Medicine at Mass General collaborate with Core investigators in translational and clinical research projects.
• Biospecimen services
  • Clinical database and patient identification
  • Biospecimen collection and processing services
  • Serum, stool and tissue biorepository services
• Data collection and analysis services
  • Regulatory services
  • Genotype and microbiome library
  • Single-cell RNA sequencing data from colonic biopsies that generated an atlas of ulcerative colitis
  • Bioinformatics support including algorithms for pathway analysis
• Access to a clinical and translational database
  • Access to clinical data for all patients with CD or UC including detailed phenotyping
  • Linkage of clinical data to genotype and microbiome features