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Barrett EsophagusPhase 2NCT04939051

Obeticholic Acid for Prevention in Barrett's Esophagus

A Phase 2 study testing Biospecimen Collection, Esophageal Biopsy and Esophagogastroduodenoscopy in people with Barrett Esophagus and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Barrett Esophagus, Esophageal Adenocarcinoma
What is being tested?
Biospecimen Collection, Esophageal Biopsy and Esophagogastroduodenoscopy
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
8 sitesUnited States
Study dates
3 Jan 2024to 1 Sep 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 %
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  • 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
  • Willing to undergo testing for human immunodeficiency virus (HIV) testing if not tested within the past 6 months
  • Willing to undergo hepatitis B and C screening if not tested within the past 6 months
  • Willing and able to adhere to the prohibitions and restrictions specified in the approved protocol
  • Willingness to moderate alcohol intake (consuming no more than 1 or 2 alcoholic drinks per day for women and men, respectively)
  • Participants must have no evidence of active or recurrent invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

8 sites in 1 country

United States8 sites, 8 recruiting

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

    Scott M. Schuetze, 734-647-8925, scotschu@med.umich.edu

    Scott M. Schuetze

    Recruiting

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

    Nicholas J. Shaheen, 919-966-7047, nshaheen@med.unc.edu

    Nicholas J. Shaheen

    Recruiting

  • Case Western Reserve University

    Cleveland, Ohio, 44106

    Amitabh Chak, 216-844-7344, amitabh.chak@uhhospitals.org

    Amitabh Chak

    Recruiting

  • Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

    Joseph E. Willis, 216-286-0151, josephe.willis@uhhospitals.org

    Joseph E. Willis

    Not yet recruiting

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

    Amitabh Chak, 216-286-0151, Amitabh.chak@uhhospitals.org

    Amitabh Chak

    Not yet recruiting

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

    Prashanthi Thota, 216-444-0780, thotap@ccf.org

    Prashanthi Thota

    Recruiting

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

    Ajay Bansal, 816-861-4700, abansal@kumc.edu

    Ajay Bansal

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Dayna S. Early, 314-454-5960, dearly@wustl.edu

    Dayna S. Early

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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 measured by visual analogue scale 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 screening and end of treatment visit and blood sample collection throughout the study.

After completion of the study treatment, patients are followed up at 14-21 days.

Being tested
Biospecimen Collection, Esophageal Biopsy, Esophagogastroduodenoscopy, Liver Ultrasonographic Elastography, Obeticholic Acid
Medical subject headings
Barrett Esophagus, Adenocarcinoma Of Esophagus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood sample collection

  • Esophageal BiopsyProcedure or surgery

    Also called Biopsy of Esophagus

    Undergo esophageal biopsy, brushings and gastric aspirate

  • EsophagogastroduodenoscopyProcedure or surgery

    Also called EGD, Upper Endoscopy

    Undergo EGD

  • Liver Ultrasonographic ElastographyProcedure or surgery

    Also called Fibroscan, TE, Transient Elastography, VCTE

    Undergo liver ultrasound with elastography

  • Obeticholic AcidBiological

    Also called INT-747, Ocaliva

    Given PO

  • Placebo AdministrationDrug

    Given PO

  • Questionnaire AdministrationOther

    Ancillary study

Study groups in NCT04939051
Study groupRoleWhat they receive
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.
Receives: Procedure: Biospecimen Collection; Procedure: Esophageal Biopsy; Procedure: Esophagogastroduodenoscopy; Procedure: Liver Ultrasonographic Elastography; Biological: Obeticholic Acid; Other: Questionnaire Administration
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.
Receives: Procedure: Biospecimen Collection; Procedure: Esophageal Biopsy; Procedure: Esophagogastroduodenoscopy; Procedure: Liver Ultrasonographic Elastography; Drug: Placebo Administration; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2021
  2. Study start3 Jan 2024
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion1 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04939051
Sponsor's protocol ID
NCI-2021-06441
Other IDs
NCI-2021-06441, UMCC 2022.048, UMI21-05-01, P30CA046592, UG1CA242632
Status last verified
Jul 2026
First submitted
24 Jun 2021
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Esophageal Biopsy and Esophagogastroduodenoscopy in people with Barrett Esophagus and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change in leucine-rich repeat-containing G-protein coupled receptor 5+ cell count (time frame: Baseline up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04939051.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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