Obeticholic Acid for Prevention in Barrett's Esophagus
5 other identifiers
interventional
30
1 country
8
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-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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2024
Typical duration for phase_2
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2021
CompletedFirst Posted
Study publicly available on registry
June 25, 2021
CompletedStudy Start
First participant enrolled
January 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
April 13, 2026
January 1, 2026
3.7 years
June 24, 2021
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Mean change in leucine-rich repeat-containing G-protein coupled receptor 5+ cell count
The mean difference in this percentage is compared across the two study arms by means of a two-sample t-test. As a further sensitivity analysis, the outcome of change will be analyzed under a linear regression model framework, controlling for factors such as age, sex, body mass index, and grade of dysplasia.
Baseline up to 6 months
Other Outcomes (9)
Measurement of obeticholic acid (OCA) and OCA metabolites in plasma
Up to 6 months
Measurement of bile acid levels in plasma, gastric juice and in Barrett's tissue
Up to 6 months
Measurement of C4 in blood
Up to 6 months
- +6 more other outcomes
Study Arms (2)
Arm I (OCA)
EXPERIMENTALPatients receive OCA PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound with elastography during screening, EGD with biopsies, brushings and gastric aspirate at screening and end of treatment visit and blood sample collection throughout the study.
Arm II (placebo)
PLACEBO COMPARATORPatients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound with elastography during screening, EGD with biopsies, brushings and gastric aspirate at screening and end of treatment visit and blood sample collection throughout the study.
Interventions
Undergo EGD
Undergo blood sample collection
Undergo esophageal biopsy, brushings and gastric aspirate
Undergo liver ultrasound with elastography
Eligibility Criteria
You may qualify if:
- 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 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%)
- Hemoglobin \>= 10g/dL or hematocrit \>= 30 %
- Leukocyte count \>= 3,500/microliter
- Platelet count \>= 100,000/microliter
- Creatinine clearance (calculated if measured is not available) \>= 30mL/min/1.73m\^2
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 X institutional upper limit of normal (ULN)
- Total bilirubin =\< 1.0 X ULN
- Alkaline phosphatase =\<1.5 X ULN
- Gamma-glutamyl transferase (GGT) =\< 1.5 X ULN
- The effects of OCA on the developing human fetus are unknown. For this reason, all men and women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of study participation, and for at least 6 months after receiving the last dose of study drug. 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. Non-English speaking participants are allowed to enroll even if they skip answering quality-of-life (QOL) questionnaires. Special efforts will be made through community advisory boards at participating sites to reach Spanish speaking participants
- +5 more criteria
You may not qualify if:
- 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:
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Prashanthi Thota
University of Michigan Rogel Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2021
First Posted
June 25, 2021
Study Start
January 3, 2024
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2027
Last Updated
April 13, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.