Malabsorption Blood Test (MBT) to Determine Exocrine Pancreatic Function and Related Quality of Life in Chronic Pancreatitis - ABSTRACT Exocrine Pancreatic Insufficiency (EPI) manifests with fat malabsorption in the setting of inadequate release of pancreatic digestive enzymes, often in the setting of inflammatory damage such as in Recurrent Acute Pancreatitis (RAP) or Chronic Pancreatitis (CP). Patients are at risk for malnutrition as they cannot properly digest dietary fat and nutrients, and simultaneously significant weight loss, sarcopenia, osteopathy, nutritional deficiencies, gastrointestinal symptoms and impaired quality of life (QOL). There exists no reliable or standardized test to detect mild to moderate pancreatic fat malabsorption or track response to treatment. Those patients with RAP or CP who do not have symptoms of steatorrhea are at risk of a missed diagnosis and development of nutritional complications. Empiric treatment with proper medication – pancreatic enzyme replacement therapy (PERT) – is infeasible due to the cost of medication. There is a clear medical need to identify patients with pancreatic fat malabsorption who will benefit from PERT therapy. In this proposal, we will identify subjects with mild to moderate EPI using the Malabsorption Blood Test (MBT) – a serum test evaluating the absorption of lipase-dependent Heptadecanoic acid versus lipase-independent Pentadecanoic Acid - and subsequently evaluate the effect of PERT therapy on QOL. Our specific aims: Aim 1. Use MBT to identify subclinical EPI and PERT responsiveness among patients with RAP and CP with no clinical symptoms of EPI. We will enroll 80 adult subjects with RAP or CP who do not have steatorrhea. Subjects will undergo an MBT before and after receiving 5 days of PERT. Primary outcome will be the prevalence of PERT response (anticipated at ~33%), defined by any increase in the Area Under the Curve (AUC) for measurement of serum Heptadecanoic Acid after receiving PERT. Aim 2. Perform a pilot randomized placebo-controlled clinical trial of PERT supplementation for 8 weeks in PERT- responders enrolled in Aim 1 to determine the effects of PERT on clinically relevant patient reported outcomes (PROs). We will randomize 24 subjects identified as PERT-responders from Aim 1 to 8 weeks of PERT or placebo therapy. Our primary outcome will be change from baseline in the PROMIS 29+2 in subjects receiving PERT compared to placebo. We hypothesize that PERT will result in improvement of QOL compared to placebo. PROMIS Gastrointestinal Scales for belly pain, bowel incontinence, constipation, diarrhea, nausea and vomiting, reflux, and gas and bloating will be assessed as secondary outcomes. This pilot study represents a major step toward the development of a reliable detection method for mild and moderate EPI in RAP or CP, and its use to assess the effectiveness of PERT. Results of this study will lead to development of a larger, appropriately powered, multicenter trial to study the benefits of PERT in patients with mild to moderate EPI.
