Simvastatin in Reducing Pancreatitis in Patients With Recurrent, Acute or Chronic Pancreatitis

NCT02743364 | Completed Phase 2 Results DMC

• 6 other identifiers: NCI-2016-00437N01-CN-2012-00035NCI2014-04-01NWU2014-04-01N01CN00035P30CA060553
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Acute Pancreatitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to up to 6 months

Secondary Outcomes (4)

• Change in the Endoscopic Ultrasound Score (EUS)

  Baseline to up to 6 months

• Serum and Pancreatic Secretions

  Baseline and 6 months

• Pancreatitis-related Readmissions

  Baseline to up to 6 months

• Change in Health-related Quality of Life.

  Baseline to up to 6 months

Study Arms (2)

Arm I (simvastatin)

EXPERIMENTAL

Patients receive simvastatin PO QD for 6 months.

Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Simvastatin

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 6 months.

Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (simvastatin); Arm II (placebo)

Placebo Administration OTHER

Given PO

Arm II (placebo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (simvastatin); Arm II (placebo)

Questionnaire Administration OTHER

Ancillary studies

Arm I (simvastatin); Arm II (placebo)

Simvastatin DRUG

Given PO

Also known as: MK 733, Synvinolin, Zocor

Arm I (simvastatin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

Southern California Permanente Medical Group

Pasadena, California, 91188, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Pancreatitis

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Seema A. Khan, MD
• Organization: Northwestern University

s-khan2@northwestern.edu

312-503-4236

Study Officials

• Marc T Goodman

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2016
• First Posted: April 19, 2016
• Study Start: September 19, 2016
• Primary Completion: October 14, 2019
• Study Completion: May 11, 2022
• Last Updated: December 13, 2022
• Results First Posted: January 4, 2022

Record last verified: 2022-05

Locations

US (5)