Fat Malabsorption in Chronic Pancreatitis

Reduced exocrine pancreatic function or pancreatic insufficiency (RPF/PI) contributes to poor
clinical outcome in a number of diseases and conditions. The incidence, mechanism and
substantial adverse clinical outcomes of pancreatic insufficiency (PI) are well known in
patients with cystic fibrosis (CF), and the life sustaining role of pancreatic enzyme
medication in CF care is well established. Much less is known about the incidence and impact
of RPF/PI in patients with chronic pancreatitis (CP). Reliable non-invasive screening or
diagnostic tests with acceptable patient burden are not available for RPF/PI.

This is a cohort study of subjects with CP who will be evaluated before and after pancreatic
enzyme medication (Creon36™) administration. A cohort of healthy subjects will serve as a
comparison group and will be evaluated only once.

Subjects with CP will receive Creon36™, a pancreatic enzyme medication, and fat and energy
absorption will be evaluated using three methods: MBT, CFA, and BC before and after
administration of Creon36™. Many patients with CP are at risk for RPF/PI yet they rarely
undergo diagnostic testing. Pancreatic enzyme medication will likely improve clinical
outcomes and quality of life in some of those with RPF/PI. A cohort of healthy volunteers
will be evaluated with the three methods to provide essential comparison data to optimize the
understanding and interpretation of the findings from the three methods and the RPF/PI cohort
with CP. There will be no intervention for the healthy cohort.

Inclusion Criteria (CP):

- Chronic pancreatitis diagnosis by gastroenterologist. Participants with CP will be
characterized based on the TIGAR-O (toxic, genetic, autoimmune, recurrent,
obstructive) etiology system, on pancreatic morphology (Cambridge criteria) when
available, and on physiological state (exocrine and endocrine function) as recommended
by the recent American Pancreatic Association Practice Guidelines4.

- Age 30-70 years old

- Evidence of at-risk for malabsorption including: 1) history of use of and response to
pancreatic enzyme medication; 2) history of unintentional weight loss; 3) history of
increased stools per week or fatty stools; and/or 4) other clinical signs or symptoms
suggestive of fat malabsorption

- In usual state of health for past two weeks including no change in medications

- Able to consume a moderate fat diet for stool evaluations

- Able to participate in the study for about four weeks with two study visits

Inclusion Criteria (Healthy Volunteers):

- Age 30-70 years old

- No known chronic disease that would affect dietary intake or fat absorption

- In usual state of health for past two weeks, with stable medications, diet and weight

- BMI from 18-29

- Able to consume a moderate fat diet for stool evaluations

- Able to participate in the study for about one week with one study visit

Exclusion Criteria (CP):

- Evidence of normal fat absorption in medical record

- Medications that alter fat absorption (i.e. orlistat, other weight loss medications,
ursodeoxycholic acid)

- Allergy to pork products

- History of intestinal blockage or fibrosing colonopathy

- History of gout, kidney disease, or high blood uric acid (hyperuricemia)

- Pregnancy or breast feeding

Exclusion Criteria (Healthy Volunteers):

- Evidence of fat malabsorption

- Medications that alter fat absorption (i.e. orlistat, other weight loss medications,
ursodeoxycholic acid)

- Pregnancy or breast feeding