A dietary intervention clinical trial to reduce inflammation and improve outcomes in chronic pancreatitis

Project Summary Chronic pancreatitis (CP) is a fibro-inflammatory syndrome of the pancreas that develops in individuals with genetic, environmental, and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. CP patients develop a number of metabolic and nutritional complications. To date, no treatment is available to reduce or reverse the inflammatory damage associated with CP, and management is limited to treating complications after they develop. Nutritional studies and strong epidemiological data provide rationale for dietary interventions to reduce inflammation and improve clinical outcomes in chronic diseases such as CP. Data from our group demonstrates a soy-enriched diet can reduce pro-inflammatory cytokines and suppressive immune populations in prostate cancer patients, and soy isoflavones can reduce immune cell activation in vitro. Carotenoids (lycopene) are suggested as the bioactive agents responsible for the health benefits of tomatoes and directly modulate inflammation. Preliminary Data: Our team has developed a novel soy-tomato juice for use in human studies, which has previously been evaluated in healthy individuals for compliance, bioavailability, and effect on blood lipids. Preliminary data in this proposal shows that administration of this soy-tomato juice to human participants (NCT03783013) is tolerable, safe, and it is feasible to analyze immune populations in the blood. Additional work from our group provides evidence this soy-tomato dietary intervention can reduce inflammation and the severity of CP in a pre- clinical animal model. We observed that a soy-tomato diet in mice with CP reduces acinar destruction and fibrosis, systemic inflammatory cytokines and immune populations, and improves physical activity levels. Impact: This pilot trial will generate evidence to demonstrate the safety, compliance, and efficacy of a soy- tomato juice to reduce inflammation, and ultimately improve clinical outcomes in participants with CP. Project Hypothesis: A novel soy-tomato dietary intervention will reduce inflammation and improve outcomes in individuals with CP. The goals of this small R01 pilot trial project are to: 1) conduct a pilot clinical trial to assess the safety and compliance of our soy-tomato dietary intervention in participants with CP, and 2) evaluate the effects of the diet on inflammation and patient-reported outcomes (PROs). We propose the following aims: Aim 1. Conduct a pilot clinical trial to demonstrate the tolerability and compliance of a soy-tomato dietary intervention in CP. Aim 2. Demonstrate the efficacy of a soy-tomato dietary intervention to reduce systemic inflammation in CP and assess preliminary data regarding improvement in patient reported outcomes. After completion of this small R01 clinical trial project, we believe the data will inform a larger clinical trial to investigate the efficacy of this soy-tomato dietary intervention to improve PROs in the CP patient population.