A research training program will be undertaken by the applicant, Daniel A. Leffler, MD, MS in the Division of Gastroenterology, Beth Israel Deaconess Medical Center (BIDMC). Dr. Leffler has gained substantial clinical and translational research experience during his residency and fellowship at BIDMC during which he has shown impressive productivity and commitment to an academic career in patient oriented research. Drs. Ciaran P. Kelly and Detlef Schuppan, both acknowledged experts in celiac disease, will serve as mentors. A mentoring committee including Drs. Lament, Cook and Freedman will meet with the applicant and the primary mentors at regular intervals to assess progress. Currently, patient care and clinical research in celiac disesae [sic] are hindered by the lack of validated non-invasive measures of disease activity. We hypothesize that a combination of disease specific surveys and biological markers will allow development of a composite index which will accurately reflect disease activity.
The specific aims of this study are;1) To develop and evaluate survey tool for use in celiac disease. Measurements will include: A. symptoms, B. gluten free diet adherence and C. health related quality of life. 2) To rigorously evaluate and compare the ability of non-invasive tests of celiac disease activity to predict change in villous height to crypt depth ratio during gluten challenge. 3) To develop a composite model of celiac disease activity using measures from aims 1 and 2 correlated with intestinal histologic change during gluten challenge. Validity will be assessed in two independant [sic] cohorts, and data from these studies will be used to design a final multi-center validation study. Dr. Leffler will also undertake training through the Harvard School of Public Health and the Harvard Clinical Research Center and in the labs of Drs. Kelly and Schuppan. This will include didactic coursework toward an MPH, and training in modern laboratory techniques. The substantial research, educational and clinical resources of BIDMC, Harvard School of Public Health, and the Clinical Research Center are committed to the applicant to ensure successful attainment of the goals of this award.
Despite great advances in our understanding of celiac disease, there is currently no validated instrument for monitoring the activity of this common disorder other than small intestinal biopsy. The identification of accurate non-invasive measures of celiac disease activity would be of great value in clinial [sic] practice, are prerequisite to the testing of new treatment modalities and may also offer insight into disease pathogenesis.
|Shah, Sveta; Akbari, Mona; Vanga, Rohini et al. (2014) Patient perception of treatment burden is high in celiac disease compared with other common conditions. Am J Gastroenterol 109:1304-11|
|Pallav, Kumar; Kabbani, Toufic; Tariq, Sohaib et al. (2014) Clinical utility of celiac disease-associated HLA testing. Dig Dis Sci 59:2199-206|
|Kabbani, Toufic A; Kelly, Ciaran P; Betensky, Rebecca A et al. (2013) Patients with celiac disease have a lower prevalence of non-insulin-dependent diabetes mellitus and metabolic syndrome. Gastroenterology 144:912-917.e1|
|Leffler, Daniel; Schuppan, Detlef; Pallav, Kumar et al. (2013) Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut 62:996-1004|
|Ludvigsson, Jonas F; Leffler, Daniel A; Bai, Julio C et al. (2013) The Oslo definitions for coeliac disease and related terms. Gut 62:43-52|
|Vanga, Rohini; Leffler, Daniel A (2013) Gluten sensitivity: not celiac and not certain. Gastroenterology 145:276-9|
|Pallav, K; Leffler, D A; Tariq, S et al. (2012) Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice. Aliment Pharmacol Ther 35:380-90|
|Kabbani, T A; Goldberg, A; Kelly, C P et al. (2012) Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet. Aliment Pharmacol Ther 35:723-9|
|Pallav, Kumar; Leffler, Daniel A; Bennett, Michael et al. (2012) Open conformation tissue transglutaminase testing for celiac dietary assessment. Dig Liver Dis 44:375-8|
|Roshan, Bakht; Leffler, Daniel A; Jamma, Shailaja et al. (2011) The incidence and clinical spectrum of refractory celiac disease in a north american referral center. Am J Gastroenterol 106:923-8|
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