The following info and data is provided "as is" to help patients around the globe.
We do not endorse or review these studies in any way.
Brief Title: Obeticholic Acid for Prevention in Barrett's Esophagus
Official Title: Obeticholic Acid for Prevention in Barrett's Esophagus
Study ID: NCT04939051
Brief 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-1β and TNFα 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.
Detailed 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 versus placebo on total and individual bile acid composition in Barrett's tissue, gastric aspirate, and serum. III. To assess the effects of treatment with OCA versus placebo on serum levels of 7alpha-hydroxy-4- cholesten-3-one (C4), a key precursor in bile acid synthesis, and fibroblast growth factor-19 (FGF-19), a fibroblast growth factor which downregulates bile acid synthesis. IV. To assess the effect of OCA on FXR expression in Barrett's tissue. V. To assess the effects of treatment with OCA versus placebo on biomarkers of the carcinogenic process - proliferation (Ki-67), apoptosis (cleaved caspase 3), and oxidative damage (8-hydroxydeoxyguanosine) as determined from Barrett's mucosal biopsies. VI. To assess the effects of treatment with OCA versus placebo on histologic changes in Barrett's samples pre and post-intervention for development/ resolution of dysplasia. VII. To assess the effects of treatment with OCA versus placebo on markers of differentiation- CDX2/SOX2/p53 expression in Barrett's tissue. VIII. To assess the safety profile of treatment with OCA versus placebo which includes incidence and severity of pruritus and changes in serum total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and triglycerides. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive OCA orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound with elastography during screening, esophagogastroduodenoscopy (EGD) with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study. After completion of the study treatment, patients are followed at 14-21 days.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: Yes
University of Kansas Cancer Center, Kansas City, Kansas, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, United States
Washington University School of Medicine, Saint Louis, Missouri, United States
UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Cleveland, Ohio, United States
University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States
Cleveland Clinic Foundation, Cleveland, Ohio, United States
Name: Dean E Brenner
Affiliation: University of Michigan Rogel Cancer Center
Role: PRINCIPAL_INVESTIGATOR