Simvastatin in Reducing Pancreatitis in Patients With Recurrent, Acute or Chronic Pancreatitis
Simvastatin in Reducing Pancreatitis in Patients With Recurrent, Acute or Chronic Pancreatitis
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.
Inclusion Criteria:

 -  At least two episodes of acute pancreatitis in the past 12 months; acute pancreatitis
 is defined any 2 of the following: (1) typical upper abdominal pain; (2) elevation in
 serum amylase or lipase >= 3 times upper limit of normal; (3) features of acute
 pancreatitis on cross-sectional imaging

 -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

 -  Leukocytes >= 2,500/microliter

 -  Absolute neutrophil count >= 1,500/microliter

 -  Platelets >= 100,000/microliter

 -  Hemoglobin > 10 g/dL

 -  Total bilirubin =< 3.0 x institutional upper limit of normal (ULN)

 -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
 [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
 =< 1.5 x institutional ULN; patients whose AST/ALT levels normalize by screen 2 after
 an abnormal test will be included in the trial

 -  Creatinine < 1.5 mg/dL

 -  Women of child-bearing potential must have a confirmed negative pregnancy test result
 prior to enrollment

 -  The effects of simvastatin on the developing human fetus at the recommended
 therapeutic dose are unknown; for this reason and because statins are known to be
 teratogenic, women of child-bearing potential and men must agree to use adequate
 contraception (hormonal or barrier method of birth control; abstinence) prior to study
 entry and for the duration of study participation; should a woman become pregnant or
 suspect she is pregnant while participating in this study, she should inform her study
 physician immediately; it is not known whether simvastatin is excreted into human
 milk; however, a small amount of another drug in this class does pass into breast
 milk; because statins have the potential for serious adverse reactions in nursing
 infants, women who receive treatment with simvastatin should not breastfeed their
 infants

 -  Ability to understand and the willingness to sign a written informed consent document
 and medical release

 -  Willing and able to comply with trial protocol and follow-up

 Exclusion Criteria:

 -  Prior or current use of statin medication, or current use of gemfibrozil,
 cyclosporine, danazol, lomitapide, verapamil, diltiazem, dronedarone, amiodarone,
 amlodipine, ranolazine, or strong cytochrome P450, family 3, subfamily A, polypeptide
 4 (CYP3A4) inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole,
 human immunodeficiency virus [HIV] protease inhibitors, boceprevir, telaprevir,
 erythromycin, clarithromycin, telithromycin, nefazodone, or cobicistat-containing
 products)

 -  History of chronic myopathy

 -  Current use of any other investigational agents

 -  History of adverse effects, intolerance, or allergic reactions attributed to compounds
 of similar chemical or biologic composition to simvastatin (i.e., other statin
 medications)

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements

 -  Women who are pregnant or breastfeeding; pregnant women are excluded from this study
 because simvastatin is a lipid-lowering agent with the potential for teratogenic or
 abortifacient effects; because there is an unknown but potential risk for adverse
 events in nursing infants secondary to treatment of the mother with simvastatin,
 breastfeeding should be discontinued if the mother is treated with simvastatin

 -  Presence of gallstones and hypertriglyceridemia (level greater than 800 mg/dl) that
 requires medical or surgical intervention; note: we will include patients who had an
 independent episode of pancreatitis after a cholecystectomy, but exclude patients who
 are candidates for cholecystectomy

 -  History of pancreatic adenocarcinoma (at any time)

 -  History of active malignancy in the past 2 years (excluding basal/squamous cell skin
 cancer or prostate cancer with a Gleason score 6 or less)

 -  Known active infection with HIV

 -  Concurrent illness, such as known psychiatric disorders or substance abuse (i.e.,
 average alcohol consumption of more than 5 drinks per day), which in the opinion of
 the investigators would compromise either the patient or the integrity of the data

 -  Laboratory (lab) results do not meet inclusion criteria

 -  Recurrent pancreatitis episode is iatrogenic (endoscopic retrograde
 cholangiopancreatography [ERCP] induced)

 -  Advanced chronic pancreatitis as determined by the following criteria: EUS score
 greater than 6, calcifications in combination with atrophy and/or dilation of >= 5 mm,
 or evidence of advanced chronic pancreatitis by computed tomography (CT) or magnetic
 resonance imaging (MRI) results in the past 12 months