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Simvastatin Treatment to Improve Patient-reported Outcomes in Patients With Chronic Pancreatitis (SMV in CP)

Primary Purpose

Recurrent Acute Pancreatitis, Chronic Pancreatitis

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Simvastatin
Placebo
Sponsored by
Cedars-Sinai Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Acute Pancreatitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18-75 at time of enrollment Diagnosis of Recurrent Acute or Chronic Pancreatitis not attributable to gallstones (i.e., suspected or definite biliary etiology), medications, trauma or autoimmune pancreatitis. For CP, imaging studies that can be used for diagnosis classification using Cambridge criteria46,47. Ability to take oral medication and be willing to adhere to the dosing regimen. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one month after administration of study medication. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one month after administration of study medication. No prior pancreatic surgery No current statin use for 6 months. Exclusion Criteria: Pregnancy or lactation History of autoimmune, medication caused or traumatic pancreatitis. Primary pancreatic tumors - pancreatic ductal adenocarcinoma, suspected cystic neoplasm (>1 cm. in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors. Pancreatic metastasis from other malignancies. History of solid organ transplant, HIV/AIDS. Known isolated pancreatic exocrine insufficiency (i.e.., in the absence of any eligible inclusion criteria). Subjects required to take itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol, amiodarone, or verapamil for other clinical indications. Current simvastatin use within the past 6 months. Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator's opinion would compromise their ability to tolerate study interventions or participate in longitudinal follow up. Patients with active liver disease. Known Pregnancy. All participants of childbearing potential, except if post-menopausal (i.e., no menses for ≥2 years) or had a hysterectomy, bilateral tubal ligation/clip (surgical sterilization) or surgical removal of both the ovaries), must have a negative urine or serum B-HCG pregnancy test documented within 2 days prior to any endoscopic or radiologic procedures done for research purposes. Any standard of care tests will follow institutional policies regarding pregnancy test. Currently incarcerated. Inability to comply with study activities.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Simvastatin

    Placebo

    Arm Description

    Participants receive Simvastatin 40mg capsule once daily for 6 months.

    Participants receive Placebo capsule matching Simvastatin once daily for 6 months.

    Outcomes

    Primary Outcome Measures

    Examine the feasibility and acceptability of testing the effect of simvastatin on health-related quality of life outcomes in patients with recurrent acute and chronic pancreatitis.
    A priori thresholds to evaluate feasibility are: 50% enrollment, <15% attrition, >75% adherence with doses, <20% side effects. A score of >75% acceptability ratings per an "Acceptability Form" that will be provided during the last visit will be used to gauge the general acceptability of the intervention (Simvastatin or Placebo) and study procedures to each participating subject.

    Secondary Outcome Measures

    Determine the effect of simvastatin treatment on health-related quality of life (QoL) outcomes in patients with recurrent acute and chronic pancreatitis.
    Health-related quality of life measurements will be collected via questionnaires (PROMIS Sleep Disturbance and Physical Short Form, Physical Distress scale, pain scales, and the Pancreatic Quality of Life Instrument) to assess overall health, quality of life, and compare the mean change from baseline across the times points 3, 6, and 12 months between the treatment group and placebo in order to identify improvement in overall quality of life and pain management. The study will also collect blood samples to look for exploratory biomarkers to identify potential measures of response to treatment with the intent do develop larger efficacy focused trials.

    Full Information

    First Posted
    February 2, 2023
    Last Updated
    July 17, 2023
    Sponsor
    Cedars-Sinai Medical Center
    Collaborators
    United States Department of Defense
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05771675
    Brief Title
    Simvastatin Treatment to Improve Patient-reported Outcomes in Patients With Chronic Pancreatitis
    Acronym
    SMV in CP
    Official Title
    Simvastatin Treatment to Improve Patient-reported Outcomes in Patients With Chronic Pancreatitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    December 2025 (Anticipated)
    Study Completion Date
    June 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Cedars-Sinai Medical Center
    Collaborators
    United States Department of Defense

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this pilot study to examine the feasibility and acceptability of simvastatin in adults with Recurrent Acute Pancreatitis (RAP) and Chronic Pancreatitis (CP).
    Detailed Description
    There are no available treatments for chronic pancreatitis (CP) or recurrent acute pancreatitis (RAP) and patients suffer with unremitting abdominal pain as the disease progress. This pilot study will test the feasibility of conducting a clinical trial of simvastatin to enhance the quality of life and delay disease progression in chronic pancreatitis patients. Emerging understanding of pancreas acinar cell organellar disorders underlying pancreatitis and the potential benefits of simvastatin to restore acinar cell homeostasis along with understanding of the pathways of the fibro-inflammatory response emanating from the disorders in the acinar cell allow the study team to propose a pilot placebo controlled double blind trial in patients with CP and RAP to test the effect of simvastatin on patient reported outcomes. Of note, RAP is a form of pancreatitis preceding CP. The Study Team hypothesizes that treatment with simvastatin will have a significant benefit for reducing pain, improving health-related quality of life (HRQoL) and pancreatitis-related outcomes in patients with CP and RAP. Changes in blood biomarkers during treatments will provide biochemical evidence for the effectiveness of the treatments. The proposed study is a pilot double blind trial with 2:1 assignment of simvastatin vs placebo. 90 patients with either CP or RAP will be enrolled over a 24-month recruitment period. Treatment with simvastatin or placebo will be for 6 months. Outcome measures will be obtained at baseline, 3 months, and 6 months and 6 months after discontinuation of treatment for a total of one year. Feasibility and adherence will be monitored. The Primary aim of this pilot study is to examine feasibility and acceptability of the trial in adults with RAP and CP. A priori thresholds to evaluate feasibility are: 50% enrollment, <15% attrition, >75% adherence with doses, <20% side effects, and >75% acceptability ratings. Multiple secondary outcome measures will be obtained that determine the effect of the treatments on pain and Quality of Life (QoL). The study plans to include male and female participants >18 years of age with Chronic and Recurrent Acute pancreatitis. Each participant will be involved for a period of 12 months from enrollment to completion of the study unless withdrawn by the study team for reasons of safety or by the participant for personal reasons.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Recurrent Acute Pancreatitis, Chronic Pancreatitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    Model Description
    Drug: Simvastatin Drug: Placebo
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    90 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Simvastatin
    Arm Type
    Experimental
    Arm Description
    Participants receive Simvastatin 40mg capsule once daily for 6 months.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants receive Placebo capsule matching Simvastatin once daily for 6 months.
    Intervention Type
    Drug
    Intervention Name(s)
    Simvastatin
    Intervention Description
    40Mg Oral Tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Matching Simvastatin Placebo tablet
    Primary Outcome Measure Information:
    Title
    Examine the feasibility and acceptability of testing the effect of simvastatin on health-related quality of life outcomes in patients with recurrent acute and chronic pancreatitis.
    Description
    A priori thresholds to evaluate feasibility are: 50% enrollment, <15% attrition, >75% adherence with doses, <20% side effects. A score of >75% acceptability ratings per an "Acceptability Form" that will be provided during the last visit will be used to gauge the general acceptability of the intervention (Simvastatin or Placebo) and study procedures to each participating subject.
    Time Frame
    End of study (12 Months)
    Secondary Outcome Measure Information:
    Title
    Determine the effect of simvastatin treatment on health-related quality of life (QoL) outcomes in patients with recurrent acute and chronic pancreatitis.
    Description
    Health-related quality of life measurements will be collected via questionnaires (PROMIS Sleep Disturbance and Physical Short Form, Physical Distress scale, pain scales, and the Pancreatic Quality of Life Instrument) to assess overall health, quality of life, and compare the mean change from baseline across the times points 3, 6, and 12 months between the treatment group and placebo in order to identify improvement in overall quality of life and pain management. The study will also collect blood samples to look for exploratory biomarkers to identify potential measures of response to treatment with the intent do develop larger efficacy focused trials.
    Time Frame
    End of study (12 Months)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18-75 at time of enrollment Diagnosis of Recurrent Acute or Chronic Pancreatitis not attributable to gallstones (i.e., suspected or definite biliary etiology), medications, trauma or autoimmune pancreatitis. For CP, imaging studies that can be used for diagnosis classification using Cambridge criteria46,47. Ability to take oral medication and be willing to adhere to the dosing regimen. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one month after administration of study medication. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional one month after administration of study medication. No prior pancreatic surgery No current statin use for 6 months. Exclusion Criteria: Pregnancy or lactation History of autoimmune, medication caused or traumatic pancreatitis. Primary pancreatic tumors - pancreatic ductal adenocarcinoma, suspected cystic neoplasm (>1 cm. in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors. Pancreatic metastasis from other malignancies. History of solid organ transplant, HIV/AIDS. Known isolated pancreatic exocrine insufficiency (i.e.., in the absence of any eligible inclusion criteria). Subjects required to take itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol, amiodarone, or verapamil for other clinical indications. Current simvastatin use within the past 6 months. Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator's opinion would compromise their ability to tolerate study interventions or participate in longitudinal follow up. Patients with active liver disease. Known Pregnancy. All participants of childbearing potential, except if post-menopausal (i.e., no menses for ≥2 years) or had a hysterectomy, bilateral tubal ligation/clip (surgical sterilization) or surgical removal of both the ovaries), must have a negative urine or serum B-HCG pregnancy test documented within 2 days prior to any endoscopic or radiologic procedures done for research purposes. Any standard of care tests will follow institutional policies regarding pregnancy test. Currently incarcerated. Inability to comply with study activities.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Bonnie Paul
    Phone
    14242793374
    Email
    Bonnie.Paul@cshs.org

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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