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Trial record 30 of 39 for:    Recruiting, Not yet recruiting, Available Studies | "Pancreatitis, Chronic"

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

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ClinicalTrials.gov Identifier: NCT02743364
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : May 10, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Acute Pancreatitis Recurrent Disease Other: Laboratory Biomarker Analysis Other: Placebo Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Simvastatin Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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 change in the endoscopic ultrasound score (EUS). II. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit

1) on change in fecal elastase. III. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit

1) on change in serum and pancreatic fluid levels of CRP, IL-6, IL-10, TGFbeta1, MMP-9, TNF-alpha, and soluble (s)-fractalkine.

IV. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit 1) on change in pancreatic fluid levels of EMT markers, e-cadherin and vimentin.

V. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit 1) on change in pancreatitis-related readmissions. VI. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit

1) on change in KRAS gene mutations in pancreatic fluid. VII. To evaluate the effect of a simvastatin intervention versus placebo at 6 months from baseline (study visit

1) on change in quality of life score as measured by the quality of life questionnaire core 30 (QLQ-C30) and quality of life questionnaire pancreatic modification (QLQ-PAN28) 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  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Statin Therapy to Reduce the Risk of Recurrent Pancreatitis
Actual Study Start Date : September 19, 2016
Estimated Primary Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatitis
Drug Information available for: Simvastatin

Arm Intervention/treatment
Experimental: Arm I (simvastatin)
Patients receive simvastatin PO QD for 6 months.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Drug: Simvastatin
Given PO
Other Names:
  • MK 733
  • Synvinolin
  • Zocor

Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for 6 months.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Change in peak bicarbonate concentration, measured using endoscopic pancreatic function test (ePFT) [ Time Frame: Baseline to up to 6 months ]
    Nonparametric two-sample Wilcoxon-Mann-Whitney test will be used.


Secondary Outcome Measures :
  1. Change in the endoscopic ultrasound score [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics and graphics will be used as well as study random effects regression trends along the timeline.

  2. Change in fecal elastase [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics and graphics will be used as well as study random effects regression trends along the timeline.

  3. Change in pancreatic fluid levels, measured by ePFT [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics and graphics will be used as well as study random effects regression trends along the timeline.

  4. Change in pancreatitis-related readmissions [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics and graphics will be used as well as study random effects regression trends along the timeline.

  5. Change in KRAS gene mutations, assessed in pancreatic fluid [ Time Frame: Baseline to up to 6 months ]
    The frequency of new KRAS mutations (not present at baseline), and frequency of reverted KRAS mutations (present at baseline but not present at follow-up) will be compared between the intervention and the placebo arm, using the Fisher's exact test.

  6. Change in quality of life measured using the quality of life questionnaire core 30 and quality of life questionnaire pancreatic modification [ Time Frame: Baseline to up to 6 months ]
    Descriptive statistics and graphics will be used as well as study random effects regression trends along the timeline.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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; 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; 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743364


Locations
United States, California
Kaiser Permanente Los Angeles Medical Center Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Bechien U. Wu    323-783-4011    Bechien.u.wu@kp.org   
Principal Investigator: Bechien U. Wu         
Cedars Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Marc T. Goodman    310-423-6188    marc.goodman@cshs.org   
Principal Investigator: Marc T. Goodman         
Stanford Cancer Institute Palo Alto Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Walter G. Park    650-723-4102    wgpark@stanford.edu   
Principal Investigator: Walter G. Park         
Southern California Permanente Medical Group Recruiting
Pasadena, California, United States, 91188
Contact: Karl K. Kwok    323-783-6830    karl.k.kwok@kp.org   
Principal Investigator: Karl K. Kwok         
United States, Pennsylvania
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Dhiraj Yadav    412-864-7078    yadavd@upmc.edu   
Principal Investigator: Dhiraj Yadav         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Marc Goodman Northwestern University

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02743364     History of Changes
Other Study ID Numbers: NCI-2016-00437
NCI-2016-00437 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
N01-CN-2012-00035
NCI2014-04-01 ( Other Identifier: Northwestern University )
NWU2014-04-01 ( Other Identifier: DCP )
N01CN00035 ( U.S. NIH Grant/Contract )
P30CA060553 ( U.S. NIH Grant/Contract )
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: May 10, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Pancreatitis
Pancreatic Diseases
Digestive System Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors