Obeticholic Acid for Barrett's Esophagus

Recruiting in Palo Alto (17 mi)

+9 other locations

Overseen by Dean E. Brenner

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must be taking: Proton pump inhibitors

Must not be taking: Bile acid sequestrants, Clozapine

Disqualifiers: Chronic liver disease, Pancreatitis, others

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of 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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot take investigational agents, certain bile acid medications, clozapine, theophylline derivatives, tizanidine, warfarin, and some hepatotoxic drugs. If you are on these, you must stop them at least 5 days before starting the trial.

What data supports the effectiveness of the drug Obeticholic Acid for Barrett's Esophagus?

Obeticholic Acid has shown effectiveness in treating liver-related conditions like primary biliary cholangitis and non-alcoholic steatohepatitis by reducing liver fat and inflammation. While this is not directly related to Barrett's Esophagus, its ability to influence liver and metabolic conditions suggests potential benefits that might be explored in other diseases.

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Is obeticholic acid safe for humans?

Obeticholic acid has been used safely in humans for conditions like primary biliary cholangitis and nonalcoholic steatohepatitis, with studies evaluating its safety in real-world settings.

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How is the drug Obeticholic Acid unique for treating Barrett's Esophagus?

Obeticholic Acid is unique because it is a farnesoid X receptor (FXR) agonist, which means it works by activating a specific receptor involved in regulating bile acids and metabolism. This mechanism is different from other treatments for Barrett's Esophagus, which may not target these pathways.

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Eligibility Criteria

This trial is for adults over 18 with Barrett's Esophagus (BE) who have been on proton pump inhibitors for at least a month. They should not have high-grade dysplasia or cancer, no history of ablative therapy in the BE segment, and must be generally healthy without chronic liver disease or uncontrolled illnesses. Participants need to use contraception and cannot be pregnant or breastfeeding.

Inclusion Criteria

Absolute leukocyte count >= 3,000/microliter

Hemoglobin >= 10g/dL

I am mostly active and can care for myself.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have had recent gallbladder inflammation or a blockage in my bile ducts.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either obeticholic acid or placebo orally once daily for 6 months

6 months

Regular visits for blood sample collection and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-3 weeks

1 visit (in-person)

Participant Groups

The trial is testing obeticholic acid (OCA), which may reduce damage from bile acids in the esophagus by activating FXR to lower bile acid levels and inflammation. It includes questionnaires, biospecimen collection, biopsies, ultrasonography, endoscopy procedures, OCA administration versus placebo.

Group I: Arm I (OCA) Experimental Treatment 6 Interventions

Patients receive OCA PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound during screening, EGD with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study.

Group II: Arm II (placebo) Placebo Group 6 Interventions

Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo liver ultrasound during screening, EGD with biopsies, brushings and gastric aspirate at end of treatment visit and blood sample collection throughout the study.

Obeticholic Acid is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Ocaliva for:

• Primary biliary cholangitis (PBC) without liver problems or with compensated cirrhosis but without portal hypertension

🇪🇺 Approved in European Union as Ocaliva for:

• Primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UNC Lineberger Comprehensive Cancer Center Chapel Hill, NC

Cleveland Clinic Foundation Cleveland, OH

Washington University in St. Louis Saint Louis, MO

University of North Carolina Chapel Hill, NC

More Trial Locations

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Obeticholic Acid: First Global Approval. [2018] Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. The drug is in preregistration for this indication in the EU. This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world experience with obeticholic acid in patients with primary biliary cholangitis. [2022] Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions.

3. England pubmed.ncbi.nlm.nih.gov

Obeticholic acid-a new therapy in PBC and NASH. [2021] Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH).

4. England pubmed.ncbi.nlm.nih.gov

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. [2022] The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis.

5. United States pubmed.ncbi.nlm.nih.gov

Modeling and Experimental Studies of Obeticholic Acid Exposure and the Impact of Cirrhosis Stage. [2018] Obeticholic acid (OCA), a semisynthetic bile acid, is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of chronic nonviral liver diseases. Physiologic pharmacokinetic models have been previously used to describe the absorption, distribution, metabolism, and excretion (ADME) of bile acids. OCA plasma levels were measured in healthy volunteers and cirrhotic subjects. A physiologic pharmacokinetic model was developed to quantitatively describe the ADME of OCA in patients with and without hepatic impairment. There was good agreement between predicted and observed increases in systemic OCA exposure in subjects with mild, moderate, and severe hepatic impairment, which were 1.4-, 8-, and 13-fold relative to healthy volunteers. Predicted liver exposure for subjects with mild, moderate, and severe hepatic impairment were increased only 1.1-, 1.5-, and 1.7-fold. In subjects with cirrhosis, OCA exposure in the liver, the primary site of pharmacological activity along with the intestine, is increased marginally (∼2-fold).

6. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. [2022] Obeticholic acid (OCA; INT-747, 6α-ethyl-chenodeoxycholic acid) is a semisynthetic derivative of the primary human bile acid chenodeoxycholic acid, the natural agonist of the farnesoid X receptor, which is a nuclear hormone receptor that regulates glucose and lipid metabolism. In animal models, OCA decreases insulin resistance and hepatic steatosis.