U-01 CONSORTIUM FOR THE STUDY OF CHRONIC PANCREATITIS,DIABETES AND PANCREATIC CANCER CLINICAL CENTERS

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The continuation of the CPDPC will require the completion of the acquisition of subjects and biospecimens, and sufficient follow-up to determine clinically relevant outcomes. Future efforts for which the CPDPC was formed include includes biomarker development and validation, drug development or repurposing, and therapeutic trials. Biomarker development and validation is needed for such purposes as early diagnosis (chronic pancreatitis and pancreatic cancer), prognosis, risk stratification and precision therapy. A second clinical need is the development of better therapies for the diabetes associated with pancreatic diseases, and better management of the pancreatic diseases themselves. We propose one biomarker study for the next phase of the CPDPC, a study of sarcopenia as a biomarker for worse outcome in patients with chronic pancreatitis. We also propose 2 potential trials for the next phase of the CPDPC, one focused on developing more effective therapy for pancreaticogenic (Type 3c) diabetes and one for a trial assessing timing of surgical intervention in painful chronic pancreatitis: 1. Finalize recruitment and follow-up of the PROCEED, DETECT, and NOD cohorts, and incorporate strategies to increase recruitment of NOD subjects. Recruitment, retention, and high quality data will need to be continued for all the cohorts. Recruitment into the NOD protocol has been most challenging. We will utilize the OneFlorida clinical data research network to identify partner health organizations within Florida to increase the pool of eligible study subjects in both NOD as well as future clinical trials. 2. Characterize the prevalence, predictors, and impact of sarcopenia in patients with acute relapsing pancreatitis and chronic pancreatitis, and the interaction with coexistent diabetes; and establish strategies to identify and treat sarcopenia in these patients. While sarcopenia has been identified as a common consequence of pancreatic cancer, the prevalence of sarcopenia and clinical impact in patients with chronic pancreatitis is of equal clinical import. 3. Implement a clinical trial within the CPDPC assessing the timing of surgical intervention in patients with painful chronic pancreatitis or relapsing pancreatitis. Pain is the most common symptom from chronic pancreatitis, the most common reason for intervention, and the most important detractor from quality of life. Medical, endoscopic, and surgical therapy are not highly effective, and the choice and timing of intervention for best outcomes is not known. A trial comparing outcomes from surgical therapy (drainage or resection) compared to endoscopic therapy in individuals with suitable anatomy who are not dependent on opioids and have not developed continuous pain is likely to identify more effective timing of therapy. 4. Determine the most effective and safest management strategy for pancreaticogenic diabetes (Type 3c) in patients with chronic pancreatitis. These individuals have a mix of insulin resistance and insulin deficiency, and may be malnourished. The lack of pancreatic islet cell counterregulatory hormones make treatment-induced hypoglycemia a very significant risk, and the coexistence of exocrine pancreatic insufficiency may nutrient absorption less predictable. We propose a cross sectional analysis of patients entered into PROCEED and DETECT cohorts, followed by a trial of two treatment approaches (current standard medical therapy, versus newly available devices for continuous glucose monitoring and insulin therapy) to determine the most effective and safest strategies. This proposed work spans critical areas of knowledge deficit: the role of sarcopenia in chronic pancreatitis and relapsing acute pancreatitis, the most effective use of interventional therapy for chronic pancreatitis pain, and the management of the complex metabolic profiles of Type3c diabetes. These potential projects, if adopted by the continuation of the CPDPC, will appropriately utilize the resources generated by the first iteration of the CPDPC and the platform of clinical centers to realize the original goals and objectives of the CPDPC.