This overall goal of this mentored patient-oriented research career development award is to improve our understanding of pouchitis and other inflammatory conditions after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Dr. Barnes is a motivated clinical researcher at the University of North Carolina at Chapel Hill (UNC), with a specific interest in the study of inflammatory bowel diseases. Over the next five years, Dr. Barnes will work with his mentorship committee to continue his progression towards his goal of independence. His mentorship committee includes experts in gastrointestinal epidemiology and comparative effectiveness (Kappelman), patient reported outcomes [(PROs) DeWalt], and precision medicine (Kosorok). Each member has an established track record of mentoring junior faculty, consistent peer-reviewed support, and high research productivity. Dr. Barnes?s career development objectives are as follows: 1) develop a new skillset in comparative effectiveness research using real-world data; 2) obtain knowledge and experience in the development of PRO assessments; 3) acquire new skills in machine learning and precision medicine principles which will allow for the incorporation of clinical and microbiota data into new risk modeling for patients undergoing restorative proctocolectomy with IPAA, and 4) transition to independence. To achieve his career development objectives, Dr. Barnes will participate in structured coursework, conduct mentored research, and will participate in workshops through the North Carolina Translational and Clinical Sciences Institute, including the R-Writing Group. The research and training environment at UNC is well established. For fiscal year 2019, UNC ranked tenth among both private and public universities nationwide for National Institutes of Health (NIH) research funding to domestic institutions of higher education.
The specific aims of this research project are 1) to evaluate the comparative effectiveness of specific biologic therapies for the treatment of chronic inflammatory conditions of the pouch after IPAA; 2) to develop PRO items for evaluating quality of life and specific symptom domains among patients after IPAA. Techniques for PRO development will include identifying symptom domains relevant to patients after IPAA using qualitative research methods, selecting candidate items for IPAA-specific PROs using existing PRO instruments where appropriate, and performing cognitive interviews with patients after IPAA to ensure content validity; and 3) to demonstrate novel methods for identifying predictors of chronic pouchitis using a machine learning approach. Expanding an existing prospective cohort, Dr. Barnes will utilize the stool microbiome, laboratory data and clinical variables to create signatures for identifying predictors of chronic pouchitis. The combination of mentorship, didactics, and research experiences offered through this K23 proposal will allow Dr. Barnes to develop a unique skillset that will aid in his ultimate transition to independence as a clinical investigator and research scientist.
Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the most common surgery for refractory ulcerative colitis and ulcerative colitis-related dysplasia, multiple complications can occur. Short and long-term complications include inflammatory conditions of the pouch such as acute and chronic pouchitis and Crohn?s-like disease of the pouch, each of which can require new medical treatments after surgery and can significantly impact the quality of life of individual patients. This mentored patient-oriented research career development project will generate evidence about the comparative effectiveness of therapies for the treatment of these inflammatory conditions of the pouch, will develop new IPAA-specific patient-reported assessments of pouch symptoms and quality of life, and will utilize precision medicine techniques including machine learning to identify patients at high-risk for developing chronic pouchitis.