Simvastatin Treatment to Improve Patient-Reported Outcomes in Patients with Chronic Pancreatitis
Abstract
Objectives and Rationale: Our Topic Area is Pancreatitis. There are no effective therapeutics for the persistent forms of pancreatitis known as Recurrent Acute Pancreatitis (RAP) and Chronic Pancreatitis (CP). These disease states are associated with severe and persistent pain associated with poor Health-Related Quality of Life (HRQoL). Based on our work including results from our current Focused Program Award, our objective is to develop treatments to relieve symptoms and improve HRQoL for patients with persistent forms of pancreatitis using a pilot double-blind placebo controlled clinical trial with simvastatin; and use preclinical models of pancreatitis to test agents we hypothesize will add to the effect of simvastatin. The pilot clinical trial will identify patient reported outcomes and blood biomarkers representing disease processes that can be used to monitor the effects of treatment on the pancreas. Proposed Expansion Based on Focused Program Work: This Expansion Award is based on our work in our current Focused Program Award. The projects of the Focused Program were designed to investigate both patient-reported factors and molecular markers that characterize pancreatitis in those drinking alcohol combined with mechanistic studies in animal models to increase our understanding of how alcohol and smoking promote pancreatitis. Results coming from the Focused Program that have direct relevance to this Expansion Award proposal include determining the mechanisms of the beneficial effects of the cholesterol-lowering agent simvastatin on alleviating pancreatitis; identification of blood-based biomarkers representing the process of disease in the pancreas; and additional agents that are very likely ones that can have additional benefits to simvastatin to treat the pancreatitis diseases. Based on our work, for the Expansion proposal we plan to: (1) Determine feasibility and acceptability of oral simvastatin (40 mg/day) in subjects with painful RAP or definite CP using a randomized controlled double-blind trial 6 months in length. During the trial measurements of pain and quality of life as well as blood-based measures of pancreatitis will provide the key and important group of measurements that will be needed for the design of a larger scale trial to establish efficacy of simvastatin treatment. (2) Use preclinical models of pancreatitis to identify if additional agents we found can inhibit the fibrosing and chronic inflammation of RAP and CP can augment the effects of simvastatin to improve treatment of these diseases. FY22 PRMRP Topic Area Addressed: Pancreatitis; our project fits the strategic goals within this Topic Area to develop and test novel treatments and develop technologies for tracking progress of associated diseases and conditions. Ultimate Applicability and Impact of the Research: Our approach provides a robust pathway to develop therapeutics for RAP and CP. We will be able to validate our trial design through focusing on feasibility; and determine potential beneficial effects of simvastatin that can be validated in subsequent efficacy-focused trials. At the same time, we acknowledge the complex pathobiologic nature of these disease states, and explore potential combined agent treatment in preclinical models that will be used in additional clinical trials. This approach will establish the direction for developing effective treatment for these diseases. The military and Veteran population will benefit because this population has higher use of both tobacco and alcohol abuse compared to the civilian population and is at risk of considerable morbidity and mortality due to pancreatitis, given its strong connection to these predisposing lifestyle factors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310150
Entities
People
- Stephen J Pandol
Organizations
- Cedars-Sinai Medical Center
- United States Army