Simvastatin in Reducing Pancreatitis in Patients With Recurrent, Acute or Chronic Pancreatitis
Condition: Acute Pancreatitis
MeSH terms: Pancreatitis
Intervention: Laboratory Biomarker Analysis; Placebo Administration; Quality-of-Life Assessment; Questionnaire Administration; Simvastatin
Intervention description: Correlative studies; Given PO; Ancillary studies; Ancillary studies; Given PO
Intervention MeSH terms: Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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