Obeticholic Acid for Prevention in Barrett's Esophagus
National Cancer Institute (NCI)
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 has shown anti-cholestatic, anti-inflammatory and anti-fibrotic effects mediated by FXR activation. It down regulates bile acid availability and decreases proinflammatory cytokine production including IL-1beta and TNFalpha in human enterocytes and immune cells. This chain of events reduces the bile acid exposure in esophagus tissue thereby limiting bile acid induced damage and dysplastic progression.
Description
PRIMARY OBJECTIVE: I. To assess the mean change from baseline in the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) + cells in the crypts of esophageal tissue among patients with Barrett's esophagus (BE) receiving 25 mg of obeticholic acid (OCA), once daily from 0 to 180 days as compared to placebo. EXPLORATORY OBJECTIVES: I. To determine OCA concentrations and concentrations of the two major active metabolites, taurine, and glycine conjugates, in plasma after dosing with OCA 25 mg to determine the concentrations reached. II. To assess the effects of treatment with OCA…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Known diagnosis of histologically-confirmed 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 at least one sample with \>= 50% intestinal metaplasia in biopsies required to satisfy the endpoints of the study * Participants are on proton pump inhibitors (PPI) therapy for \>= 28 days duration * Age \>= of 18 years. Because no dosing or adverse event (AE) data are currently available…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureEsophageal Biopsy
Undergo esophageal biopsy, brushings and gastric aspirate
- ProcedureEsophagogastroduodenoscopy
Undergo EGD
- ProcedureLiver Ultrasonographic Elastography
Undergo liver ultrasound with elastography
- BiologicalObeticholic Acid
Given PO
- DrugPlacebo Administration
Given PO
- OtherQuestionnaire Administration
Locations (8)
- University of Kansas Cancer CenterKansas City, Kansas
- University of Michigan Rogel Cancer CenterAnn Arbor, Michigan
- Washington University School of MedicineSt Louis, Missouri
- UNC Lineberger Comprehensive Cancer CenterChapel Hill, North Carolina
- Case Western Reserve UniversityCleveland, Ohio
- Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer CenterCleveland, Ohio