Obeticholic Acid for Prevention in Barrett's Esophagus

Exclusion Criteria

• •History of prior ablative therapy such as radiofrequency ablation, cryotherapy or argon plasma coagulation (APC) in BE segment
• •Prior use of OCA
• •Prior history or presence of high-grade disease (HGD) or cancer on pre-intervention endoscopy
• •Cutaneous diseases manifesting with severe pruritus
• •Individuals with active, known or suspected chronic liver disease including cirrhosis, nonalcoholic steatohepatitis (NASH) with fibrosis or cirrhosis, primary sclerosing cholangitis, biliary atresia
• •Individuals with acute cholecystitis (defined by a syndrome of right upper quadrant pain, fever, and leukocytosis associated with gallbladder inflammation)
• •Individuals with a history of pancreatitis or pancreatic abnormalities
• •Individuals with hepatic steatosis and velocity \> 1.7 m/sec as determined by liver ultrasound elastography. Results of a right upper quadrant ultrasound with elastography performed within 6 months of starting study treatment may be used to assess this criteria
• •Individuals with hyperlipidemia that is not well controlled with the use of pharmacotherapy and/or dietary modifications
• •History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
• •Individuals with known hypersensitivity, allergies, or intolerance to the study drug or compounds of similar chemical or biologic composition
• •Any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures
• •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •Individuals with active and untreated hepatitis C virus (HCV) and/or or hepatitis B virus (HBV) infection
• •Individuals with HIV infection are eligible for participation if:
• •* CD4+ count \>= 300/uL
• •* Viral load is undetectable
• •* Receiving highly active antiretroviral therapy (HAART) without known or suspected drug interactions with OCA
• •* Consultation with the participant's infectious disease specialist may be obtained
• •Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 5 half-lives days prior to starting OCA or placebo on this study. Consultation with the participant's primary care provider may be obtained but is not required.
• •* The use of the following drugs or drug classes is prohibited during OCA/placebo treatment
• •* Investigational agents;
• •* Bile acid sequestrants (bile acid binding resins): cholestyramine, colestipol, or colesevelam;
• •* Bile salt efflux pump (BSEP) inhibitors;
• •* Clozapine;
• •* Theophylline derivatives;
• •* Tizanidine;
• •* Warfarin;
• •* Hepatotoxic drugs such as amiodarone, sodium valproate, certain herbal/dietary supplements, and long-term doxycycline or tetracycline
• •Pregnant, breast-feeding, or women of childbearing potential unwilling to use a reliable contraceptive method. Pregnant women are excluded from this study because OCA is an agent with unknown effects on the developing human fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA
• •Participants may not be receiving any other investigational agents