This is an application for renewal of Clinical Center designation of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). The Greater Los Angeles Clinical Center has provided considerable leadership in the organization and progress of the CPDPC. Dr. Pandol serves as co-chair of the Steering Committee and Dr. Goodarzi co-chairs the Type 3c Working Group. We have excelled in recruitment and retention of participants in the cohort studies implemented through the CPDPC designed to elucidate the natural history and develop means of diagnosis, treatment and clinical management of chronic pancreatitis (CP) and its complications in children and adults, and to determine the pathogenic interrelationships of diabetes and pancreatic cancer and develop the means of early diagnosis and management of pancreatic cancer. In addition, we have been performing a number ancillary and associated studies to support the overall goals of CPDPC, including: 1. Epidemiologic studies defining risk factors for pancreatic cancer and the natural history of CP; 2. Determining that genetic susceptibility for type 2 diabetes is a strong risk factor for diabetes associated with CP; 3. Developing liquid biopsy assays for aiding in the diagnosis of pancreatic cancer and CP; 4. Investigating mechanisms of pancreatitis and pancreatic cancer for rational pharmaceutical treatments; and 5. Conducting pilot clinical trials for treatment of recurrent acute and chronic pancreatitis. For the next phase of the CPDPC we are committed to the following Specific Aims: 1. Continue recruitment and retention of subjects in CPDPC cohort studies (PROCEED, INSPPIRE 2, NOD, DETECT) in existing and additional study sites, as well as increase diversity in the study population. 2. Continue currently supported ancillary studies to further develop risk factor models combined with liquid biopsy assays for early diagnosis of chronic pancreatitis and pancreatic cancer, and advance mechanism- based treatments and clinical trials for recurrent acute and chronic pancreatitis and pancreatic cancer. 3. Build models that combine clinical features with genetic susceptibility to allow the prediction of future development of diabetes in patients with chronic pancreatitis. 4. Determine the role of pancreatic enzyme replacement in regulating glucose homeostasis in patients with chronic pancreatitis and diabetes, with or without pancreatic exocrine insufficiency. 5. Use existing and annotated pre-diagnostic CT scans to develop artificial intelligence-based techniques for highly sensitive and specific methods for CT-based early pancreatic cancer detection. Our Center involves Cedars-Sinai Medical Center, UCLA Medical Center, the VA Greater Los Angeles Healthcare System and the University of Southern California/Los Angeles Public Health System with an organizational structure designed to expand recruitment into cohort studies of CPDPC with increased diversity and to facilitate our participation in ancillary studies.

Public Health Relevance

This is an application to renew the ?Greater Los Angeles Clinical Center of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer,? which consists of an expert team well-qualified to carry out studies of the Consortium in Los Angeles County, the most populous and ethnically diverse county in the United States. We plan to adjust and expand our recruitment strategies for cohort studies of the Consortium to help meet national goals; we will also continue progress on a series of ancillary studies within the Consortium designed to detect and treat pancreatic diseases. In addition, we propose new studies to develop prediction models for diabetes in chronic pancreatitis, interrogate the role of digestive enzyme insufficiency in this form of diabetes, and develop novel imaging-based methods for early pancreatic cancer detection that will, in turn, decrease the morbidity of pancreatic cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01DK108314-06S1
Application #
10263513
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Unalp-Arida, Aynur
Project Start
2015-09-28
Project End
2025-06-30
Budget Start
2020-09-03
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
Waldron, Richard T; Lugea, Aurelia; Gulla, Aiste et al. (2018) Proteomic Identification of Novel Plasma Biomarkers and Pathobiologic Pathways in Alcoholic Acute Pancreatitis. Front Physiol 9:1215
Uc, Aliye; Perito, Emily R; Pohl, John F et al. (2018) INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort Study: Design and Rationale for INSPPIRE 2 From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas 47:1222-1228
Hart, Phil A; Andersen, Dana K; Mather, Kieren J et al. (2018) Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: Rationale and Methodology for the DETECT Study From the Consortium for the Study of Chronic Pancreatitis Pancreas 47:1239-1243
Eibl, Guido; Cruz-Monserrate, Zobeida; Korc, Murray et al. (2018) Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer. J Acad Nutr Diet 118:555-567
Manegold, Philipp; Lai, Keane K Y; Wu, Yongfeng et al. (2018) Differentiation Therapy Targeting the ?-Catenin/CBP Interaction in Pancreatic Cancer. Cancers (Basel) 10:
Serrano, Jose; Andersen, Dana K; Forsmark, Christopher E et al. (2018) Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer: From Concept to Reality. Pancreas 47:1208-1212
Forsmark, Christopher E; Andersen, Dana K; Farrar, John T et al. (2018) Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Summary of the Working Group on Drug Development and Trials in Chronic Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 47:1200-1207
Fisher, William E; Cruz-Monserrate, Zobeida; McElhany, Amy L et al. (2018) Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas 47:1213-1221
Birtolo, Chiara; Pham, Hung; Morvaridi, Susan et al. (2017) Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration. Am J Pathol 187:146-155
Lew, Daniel; Afghani, Elham; Pandol, Stephen (2017) Chronic Pancreatitis: Current Status and Challenges for Prevention and Treatment. Dig Dis Sci 62:1702-1712

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