Health TrialsbyHealthPanel

Obeticholic Acid for Prevention in Barrett's Esophagus

ConditionsBarrett EsophagusEsophageal Adenocarcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Esophageal Biopsy

    Procedure/Surgery

    Undergo esophageal biopsy, brushings and gastric aspirate

  • Esophagogastroduodenoscopy

    Procedure/Surgery

    Undergo EGD

  • Liver Ultrasonographic Elastography

    Procedure/Surgery

    Undergo liver ultrasound with elastography

  • Obeticholic Acid

    Biological/Vaccine

    Given PO

  • Placebo Administration

    Drug

    Given PO

  • Questionnaire Administration

    Other intervention

    Ancillary study

Treatment groups

30 Participants
are divided into 2 treatment groups
Group A: Arm I (OCA)Experimental treatment 6 interventions
Group B: Arm II (placebo)Placebo comparator 6 interventions

Trial outcomes

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.

Time frame
Baseline up to 6 months

Secondary outcomes

Other outcomes

1

Measurement of obeticholic acid (OCA) and OCA metabolites in plasma

These experiments will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using a specific, sensitive and reliable tandem mass spectrometry (ultraperformance liquid chromatography- tandem mass spectrometry \[UPLC-MS/MS\]) method. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is linear mixed models (LMM) with time, group, and time-by-group interaction as primary covariates.

Time frame
Up to 6 months
2

Measurement of bile acid levels in plasma, gastric juice and in Barrett's tissue

These experiments will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using a specific, sensitive and reliable UPLC-MS/MS method to quantify the bile acid and conjugated metabolite concentration in human plasma and tissue samples. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Time frame
Up to 6 months
3

Measurement of C4 in blood

This experiment will be performed in the consortium's pharmacokinetics/Pharmacodynamics Core Laboratory at the University of Michigan LAO using UPLC-MS/MS. The blood based markers will be analyzed using a linear mixed model with study group as the primary between-subjects factor, and time (3-levels) along with the group-by-time interaction as the primary within-subjects factor. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Time frame
Up to 6 months
4

FGF-19 analysis

FGF19 concentrations will be assayed using the solid-phase enzyme-linked immunoabsorbant assay Quantikine FGF19 Immunoassay (R\&D Systems, Minneapolis, Minnesota) in the Immunology Core facility at the University of Michigan Rogel Cancer Center. The exploratory outcomes are continuous, measured at either two or three time points. The most common framework for analyzing such longitudinal data is LMM with time, group, and time-by-group interaction as primary covariates.

Time frame
Up to 6 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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