Optimizing a Novel Intraductal Delivery of Calcineurin Inhibitors as a Radiocontrast Infusion Formulation to Prevent Post-ERCP Pancreatitis
Abstract
An endoscopic retrograde cholangiopancreatography (ERCP) is a common and life-saving gastrointestinal (GI) procedure that is performed in almost half a million American each year. It was found that about 3-15% of patients underwent ERCP developed post-ERCP pancreatitis (PEP), the most common adverse effect of ERCP. However, and the efficacy and practical use of the current preventative modalities against PEP are still debated. The present project funded by Award W81XWH-19-1-0683 was proposed based on our recent discovery of an important signaling pathway for PEP mediated via the activation of the calcium-activated phosphatase calcineurin (Cn). It aims to optimize a novel intraductal delivery of Cn inhibitors as a radiocontrast infusion formulation to prevent post-ERCP pancreatitis. We designed to perform two specific aims, (1) determining the safety profile of the Cn inhibitor-RC formulations delivered via an intraductal route and (2) evaluating the efficacy of the intraductal Cn inhibitor-RC formulations to test our hypothesis that the Cn inhibitor-RC formulations were safe for use in ERCP and would prevent PEP in both clinical situations of ERCP with pancreatic duct injection as well as biliary duct injection. Our proposed project has been progressing smoothly. Due to the COVID-19 pandemic and related social distancing policy, we postponed rabbit safety testing (which usually requires two or more researchers working together) and efficacy studies to the second and third project years. Instead, we have conducted systemic safety studies in mice, which were originally proposed for the second and third project years in the grant proposal.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1118329
Entities
People
- Asna Khalid
- Mang Yu
- Sohail Z Husain
Organizations
- Stanford University