This randomized phase II trial studies how well simvastatin works in reducing pancreatitis (the inflammation of the pancreas) in patients with pancreatitis that occurs more than once (recurrent), has worsened quickly (acute), or has persisted or progressed over a long period of time (chronic). Simvastatin may decrease the inflammation of the pancreas by modulating the immune response responsible for inflammation. It is not yet known if simvastatin may be an effective treatment for pancreatitis.
PRIMARY OBJECTIVE: I. To evaluate the effect of a simvastatin intervention versus placebo on the change in secretin-stimulated peak bicarbonate concentration in the pancreatic fluid at 6 months post-treatment in patients with a history of at least two episodes of acute pancreatitis in the past 12 months. SECONDARY OBJECTIVES: I. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit 1\) on: Ia. Change in the endoscopic ultrasound score (EUS). Ib. Change in serum and pancreatic fluid levels of cytokines, chemokines, and adhesion molecules. Ic. Change in pancreatitis-related readmissions. Id. Change in quality of life score as measured by the Quality of Life (QLQ)-Core (C)30 and QLQ-Pancreatic modification (PAN)28(Chronic Pancreatitis \[CP\]). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive simvastatin orally (PO) once daily (QD) for 6 months. ARM II: Patients receive placebo PO QD for 6 months. After completion of study treatment, patients are followed up at 30, 60, and 90 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
8
Correlative studies
Given PO
Ancillary studies
Kaiser Permanente Los Angeles Medical Center
Los Angeles, California, United States
Cedars Sinai Medical Center
Los Angeles, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Southern California Permanente Medical Group
Pasadena, California, United States
Change in Peak Bicarbonate Concentration, Measured Using Endoscopic Pancreatic Function Test (ePFT)
Change in peak bicarbonate level (mmol/l) from baseline up to 6 months. Decreased peak bicarbonate concentration indicates worsening pancreatic function.
Time frame: Baseline to up to 6 months
Change in the Endoscopic Ultrasound Score (EUS)
Change in EUS score (0-96) from baseline to up to 6 months. EUS Score is a measure of pancreatitis by the presence or absence of nine ductal and parenchymal criteria for CP: hyperechoic foci, hyperechoic strands, cysts, lobularity, calcifications, hyperechoic duct margins, visual side branches, main pancreatic duct dilation, and main pancreatic duct irregularity, which sum to a score ranging from 0 to 96. Presence of 6 or more standard criteria indicates advanced chronic pancreatitis. A positive score indicates an improvement. A negative score indicates a reduction.
Time frame: Baseline to up to 6 months
Serum and Pancreatic Secretions
Expression of three biomarkers, HGF (hepatocyte growth factor), Resistin, and FASL (Fas ligand) in fluorescent intensity (arbitrary units), as an estimate of immune analyte concentration.
Time frame: Baseline and 6 months
Pancreatitis-related Readmissions
Number of participants with pancreatitis-related hospital readmissions.
Time frame: Baseline to up to 6 months
Change in Health-related Quality of Life.
Change in health-related quality of life scores (1-100) from baseline to up to 6 months measured by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-PAN28(CP) scores. A positive value indicates improvement and a negative value indicates reduction.
Time frame: Baseline to up to 6 months
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Ancillary studies
Given PO
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States