Duloxetine in Patients With Suspected Functional Pancreatic/Biliary Pain (Sphincter of Oddi Dysfunction)

SOD is a disorder involving the bile duct or pancreas causing a burning pain or cramping in
the epigastric (upper stomach) area that can radiate (spread) to the back or under the right
shoulder blade. This discomfort is thought to be caused by tightening of the Sphincter of
Oddi, which is the muscle opening that controls the flow of bile and juices from the
pancreas (enzymes) into the small intestine. It can also be caused by contractions of the
common bile duct (the duct that allows bile from the liver into the small intestine).

The purpose of this research is to study how well a medication called Duloxetine works when
used to treat pain associated with SOD. Duloxetine (also called Cymbalta) is a medication
approved by the FDA for the treatment of depression and for the treatment of pain caused by
nerve damage associated with diabetes. However, for the purposes of this research,
Duloxetine is considered investigational (experimental) since it will test how well this
medication works for the treatment of pain associated with SOD. (Cymbalta replaced with
Duloxetine in remainder of consent as requested).

PRIMARY OBJECTIVE

● Treatment effect as measured by the global assessment of change (PGIC) after 3 months of
treatment with duloxetine.

SECONDARY OBJECTIVES

- Toleration of the medication as measured by the duloxetine compliance rate;

- Safety as recorded by adverse events (AEs)

- Effect of treatment on pain reduction as measured by a pain burden assessment tool
(RAPID 3 & RAPID 1-Month);

- Effect of treatment on quality of life (QOL) as measured by the SF-36.

INCLUSION CRITERIA:

- Patients referred to MUSC pancreatico-biliary service for investigation/ mgt of
functional upper abdominal pain symptoms;

- No clinically significant medical condition(s) as determined by the investigator;

- Symptom severity. At least 2 pain attacks in the previous month, with severity of at
least 4/10 on the RAPID Start scale;

- Prior cholecystectomy;

- Age 18-65*;

- Functional pain characteristics as defined by Rome III Criteria;

- Structural causes of pain excluded by standard imaging and laboratory investigations;

- No clinically significant ECG results as determined by the investigator;

- All patients will give verbal and written Informed consent;

- Female patients must use an acceptable form of contraception, or be 2 years
postmenopausal or surgically sterile*; and

- Geographically accessible for follow-up visits

EXCLUSION CRITERIA:

- History of/current psychosis, bipolar disorder, suicidal ideation or judged to be a
significant suicide risk, as determined via baseline psychiatric assessment utilizing
the MINI interview

- History of alcohol or any psychoactive substance abuse or dependence within the past
6 months, as determined via baseline psychiatric assessment utilizing the MINI
interview

- Abnormal Liver Function Tests (> 3 x ULN)

- Known hypersensitivity to Duloxetine or any of the inactive ingredients

- Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization
or potential need to use an MAOI during study or within 5 days of discontinuation of
study drug

- Treatment with fluoxetine (deleted MAOI) within 30 days of medication start date

- Treatment with excluded medications within 7 days prior to study medication start-up
date

- Serious medical illness, including any cardiovascular, hepatic, renal respiratory
hematologic, endocrinologic or neurologic disease, or significant laboratory
abnormality as judged by study physician/investigator.

- Uncontrolled narrow-angle glaucoma

- Acute liver injury (such as hepatitis) or severe cirrhosis

- Prior lack of tolerability to duloxetine

- Pregnancy and breastfeeding

Participation in the study is approximately 4 months. There are 4 clinic visits and 2
telephone visits.