The current project aims to evaluate a new therapy for acute pancreatitis in a pilot clinical trial. Pancreatitis has been identified as a topic area for FY20 PRMRP. Furthermore, development of novel therapies for the treatment of pancreatitis is also an Area of Encouragement.

Acute pancreatitis (AP) is an inflammatory disorder of the pancreas. It is a major cause of healthcare cost in United States. Patients with AP present with severe abdominal pain. While most patients with AP get better by supportive treatment like intravenous fluids and pain medications, up to 20% of patients with AP develop severe disease characterized by severe inflammation, multi-organ damage, and very high risk of death. Currently, there is no specific treatment for patients with severe AP. The only way to change outcome for the patients with severe AP is to develop therapies that can decrease inflammation. Smoking, alcoholism, and drug abuse are the key risk factors for development of AP. Military personnel and Veterans are very susceptible and at a very high risk of developing AP, as alcohol intake, smoking and drug abuse have been commonly observed in this population.

The Principal Investigator (PI) of the current grant has demonstrated in his laboratory that pirfenidone, a novel anti-inflammatory molecule is very effective against animal models of AP. These results from animal studies are very exciting for two reasons. (1) Pirfenidone was tested in animal models of severe AP. This is important since it is the patients with severe acute pancreatitis who are at the highest risk of death and injury and urgently need novel treatment. Thus, these findings will apply to these unfortunate patients. (2) The treatment with pirfenidone in the animal studies was started when the inflammation was at the peak. These studies thus mirrored the clinical presentation of the patients with AP, as when patients with AP seek medical attention, the AP is already advanced, and inflammation is at peak. This is important, and sets apart our studies from others in the literature, where various agents are started even before AP is induced in animals. For these reasons, we have confidence that pirfenidone is ready to be tested against AP in a clinical trial. Furthermore, the fact that pirfenidone is already approved for clinical use in patients with idiopathic pulmonary fibrosis (IPF) facilitates the execution of this clinical trial. Based on our data, we have put together a clinical trial for the evaluation of safety, tolerability, and efficacy of pirfenidone in patients with severe AP.

In the current study, we will conduct a clinical trial to test the safety, tolerability, and efficacy of pirfenidone in improving AP in patients with severe disease. This clinical trial will be performed at two major academic centers, namely, University of Alabama at Birmingham (UAB) and Mayo Clinic, Rochester. We have put together a strong study team to ensure the success of this clinical trial. The PI of the current grant, Dr. Dudeja, has extensively studies pirfenidone in laboratory and has generated all the data that form the basis of the current clinical trial. The Co-PI, Dr. Vege, is a world-renowned clinical expert in acute pancreatitis and has run two successful clinical trial of drugs in AP. The Co-I, Dr. Charles Mel Wilcox, is a world-renowned expert in the management of AP and has a busy clinical pancreas practice at UAB. Finally, we have Dr. Marilyn Glassberg, PI on the original clinical trial of pirfenidone in IPF, as a Co-I on our grant. The expertise of our team members provides confidence that we will be able to execute this clinical study without difficulty.

Successful execution of the propose studies will lead to emergence of pirfenidone as the first disease-modifying treatment for acute pancreatitis. Thus, the proposed studies are very translational and have the potential to revolutionize the treatment of AP. Development of novel treatments for AP will improve the outcome of a large U.S. patient population including Veterans and military personnel suffering from this formidable disease.