Obeticholic Acid for Prevention in Barrett's Esophagus

• Status: Not yet recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the effect of obeticholic acid in treating patients with Barrett's esophagus. Bile acids present in duodenogastroesophageal reflux contribute to neoplastic progression in Barrett's esophagus. Obeticholic acid, may help increase bile flow from the liver while suppressing bile acid production, therefore reducing the exposure of the liver to toxic levels of bile acids which is potentially linked to cancer development.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

• Known diagnosis of histologically-confirmed diagnosis of BE with either no dysplasia, indefinite for dysplasia or low-grade dysplasia as defined by the presence of specialized columnar epithelium on histology and >= 2 cm of involvement on endoscopy

• Adequate Barrett's mucosa, which is defined as >= 1 out of 4 research samples (i.e. >= 25 %) with >= 50% intestinal metaplasia in biopsies required to satisfy the endpoints of the study

• Participants are on proton pump inhibitors (PPI) therapy for >= 1 month duration

• Age >= of 18 years. Because no dosing or adverse event (AE) data are currently available on the use of OCA in participants < 18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

• Absolute leukocyte count >= 3,000/microliter

• Hemoglobin >= 10g/dL

• Platelets >= 100,000/microliter

• Total bilirubin =< 1.5 X normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 X institutional upper limit of normal

• Creatinine =< 1.5 X institutional upper limit of normal

• Prothrombin time/ international normalized ratio (INR) =< 1.5 X institutional upper limit of normal

• LDL, VLDL =< 2 X institutional upper limit of normal

• HDL >= 1 X institutional lower limit of normal

• The effects of OCA on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

• Ability to understand the study procedures, benefits and risks, and sign a written informed consent document

Exclusion Criteria:

• No 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 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, 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 diagnosed within the prior 6 weeks) or biliary obstruction (defined by extrahepatic cholestasis)

• Individuals with uncontrolled dyslipidemia

• Individuals with uncontrolled coronary artery disease

• Healthy volunteers may not enroll in the study

• Participants may not be receiving any other investigational agents

• History of allergic reactions attributed to ursodeoxycholic acid

• 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

• Pregnant women are excluded from this study because the limited available human data on the use of OCA during pregnancy are not sufficient to inform a drug-associated risk. There is no information on the presence of OCA in human milk, the effects on the breastfed infant or the effects on milk production. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with OCA, breastfeeding should be discontinued if the mother is treated with OCA

• Concurrent use of:

• Bile acid binding resins such as cholestyramine, colestipol, or colesevelam (may reduce the absorption, systemic exposure, and efficacy of OCA)

• Warfarin (INR decreases following coadministration of warfarin and OCA)

• CYP1A2 substrates with narrow therapeutic index (clozapine, theophylline and tizanidine)

• Inhibitors of bile salt efflux pump (cyclosporine may exacerbate accumulation of conjugated bile salts including taurine conjugate of OCA in the liver)