The current project aims to evaluate a new therapy for recurrent acute pancreatitis in clinical trial. Pancreatitis has been identified as a topic area for Fiscal Year 2022 (FY22) Peer Reviewed Medical Research Program (PRMRP). Furthermore, development of novel therapies for the treatment of pancreatitis is also a Strategic Goal.

Acute pancreatitis is an inflammatory disorder of the pancreas. It is a major cause of health care cost in United States. Patients with acute pancreatitis presents with severe abdominal pain. While most patients with acute pancreatitis get better by supportive treatment and do not need any further treatment, up to 30% of patients will develop repeated episodes of pancreatitis. These patients are labeled to have recurrent acute pancreatitis. Not only these recurrent bouts of pancreatitis lead to unnecessary suffering, these patients are at high risk of death, decreased quality of life, and high risk of progression to chronic pancreatitis, a disease characterized by chronic pain, lack of digestive enzymes, malnutrition, diabetes, and increased risk of cancer.

Currently, there is no specific treatment, which can prevent future bouts of pancreatitis in patients with recurrent acute pancreatitis. Smoking, alcoholism, and drug abuse are the key risk factors for development of pancreatitis. Military personnel and Veterans are very susceptible and at a very high risk of developing pancreatitis, 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 pancreatitis. These results from animal studies are very exciting for multiple reasons. (1) Pirfenidone treatment not only prevents development of pancreatitis, but even if pancreatitis was to develop, pirfenidone treatment reduces its severity. (2) Furthermore, pirfenidone treatment of animals, which have recurrent episodes of pancreatitis, reduces the progression of this disease to chronic pancreatitis with its associated sequelae. These studies thus mirrored the clinical presentation of the patients with recurrent acute pancreatitis. Furthermore, the fact that pirfenidone is already approved for clinical use in patients with idiopathic pulmonary fibrosis 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 recurrent acute pancreatitis.

In the current study, we will conduct a clinical trial to test the safety, tolerability, and efficacy of pirfenidone in improving recurrent acute pancreatitis. This clinical trial will be performed at three major academic centers, namely, University of Alabama at Birmingham; Mayo Clinic, Rochester; and Brigham and Women’s Hospital. 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 studied pirfenidone in laboratory and has generated all the data that forms the basis of the current clinical trial. The Co-PI, Dr. Vege, is a world-renowned clinical expert in pancreatitis and has run two successful clinical trial of drugs in acute pancreatitis. The Co-Investigators, Drs. Julia McNabb-Baltar and Charles Mel Wilcox, are also world-renowned experts in the management of pancreatitis and have busy clinical pancreas practices. The expertise of our team members provides confidence that we will be able to execute this clinical study without difficulty.

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