Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia

Clinical Study of Ursodeoxycholic Acid in Barrett's Patients

This pilot phase II trial studies how well ursodiol works in treating patients with Barrett esophagus or cells that look abnormal under a microscope but are not cancer (low-grade dysplasia). Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ursodiol may keep cancer for forming in patients with Barrett esophagus or low-grade dysplasia.

Study Overview

• Status: Completed
• Conditions: Barrett Esophagus; Esophageal Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Ursodiol

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the ability of UDCA (ursodiol) treatment to reverse oxidative deoxyribonucleic acid (DNA) damage in the esophageal epithelium of subjects with Barrett's esophagus.

SECONDARY OBJECTIVES:

I. To determine the effects of UDCA treatment on gastric bile acid composition and on cell proliferation in Barrett's epithelium.

OUTLINE:

Patients receive ursodiol orally (PO) twice daily (BID) for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Health Sciences Center
    • Tucson, Arizona, United States, 85723
      • Southern Arizona Veterans Affairs Health Center
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center-North Campus
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Barrett's esophagus with histologically-confirmed intestinal metaplasia anywhere in the tubular esophagus either with >= 2 cm of involvement or with a minimum circumferential Barrett's esophagus (BE) length of 1 cm
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 2.0 mg/dL
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2 X institutional upper limit of normal (ULN)
• Creatinine =< 1X ULN
• Women of child-bearing potential (i.e., not surgically sterile or less than one year since last menstrual period) agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; women of childbearing potential must have a negative urine pregnancy test within 14 days prior to study agent administration; male subjects must agree to use adequate contraception (barrier method, abstinence, subject has had vasectomy or partner is using effective birth control or is postmenopausal)
• Ability to understand and the willingness to sign a written informed consent document
• Agree to refrain from any non-steroidal anti-inflammatory drug (NSAID) with the exception of low-dose aspirin (81 mg once daily [QD]) during the entire study period
• Agree not to take aluminum-containing antacids and anion exchange resins such as cholestyramine, colestimide or colestipol within 2 hours of taking UDCA

Exclusion Criteria:

• Barrett's esophagus with high grade dysplasia or carcinoma at enrollment
• Medical conditions which would make completing endoscopies or completing the trial difficult including but not limited to previous transient ischemic attacks or cerebral vascular disease, severe respiratory disease, severe ischemic heart disease or myocardial infarction in the previous 6 months, inflammatory bowel disease
• Participants may not be receiving any other investigational agents within 1 month of study enrollment
• Have used NSAID for more than 5 days per month within 1 month of enrollment except low dose aspirin (81 mg QD)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to UDCA
• 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
• Pregnant and breastfeeding women are excluded from this study; breastfeeding should be discontinued during treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Have had major upper gastrointestinal (GI) surgeries within 6 months of enrollment including, but not limited to, fundoplication, bariatric surgery, cholecystectomy
• Erosive esophagitis detected at the baseline endoscopy
• Participants who need concurrent chemotherapy, radiotherapy, or cancer-related hormonal or immunotherapy during the time of study
• Participants who have had chemotherapy, radiotherapy, or cancer-related hormonal or immunotherapy within 18 months of the baseline visit
• Current or planned use of anticoagulant drugs including, but not limited to, warfarin, heparin, low molecular weight heparin, Plavix, or Aggrenox
• Use of cyclosporine during the time of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (ursodiol); Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Ursodiol; Given PO; Other Names: UDCA; Actigall; Deursil; URSO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversal of Oxidative DNA Damage as Assessed by Changes in 8-hydroxy-2' -Deoxyguanosine (8OHdG) Immunostaining	8OHdG will be assessed by percentage of positively stained nuclear area. A paired t-test at a one-sided 0.05 significance level will be used to assess change during intervention. The observed results will be reported along with the corresponding confidence intervals.	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Gastric Bile Acid Composition (Change in Percent of Total Bile Acid Present as Ursodeoxycholic Acid and Its Glycine/Taurine Conjugates) Measured by Liquid Chromatography-tandem Mass Spectrometry, From Baseline to Post-intervention		Baseline and 6 months
Changes in Gastric Bile Acid Composition (Change in Percent of Total Bile Acid Present as Deoxycholic Acid and Its Glycine/Taurine Conjugates) Measured by Liquid Chromatography-tandem Mass Spectrometry, From Baseline to Post-intervention		Baseline and 6 months
Changes in Cell Proliferation in BE Epithelium From Baseline to Post-intervention as Assessed by Proliferation-related Ki-67 Antigen (Ki67) Immunostaining, Percentage of Positively Stained Nuclei, in BE Tissue Sections	Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.	Baseline and 6 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Bhaskar Banerjee, University of Arizona Health Sciences Center

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (Estimate): April 1, 2010

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Precancerous Conditions; Esophageal Neoplasms; Barrett Esophagus; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: NCI-2012-00450 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA023074 (U.S. NIH Grant/Contract); CDR0000669111; 09-0141-03 (Other Identifier: University of Arizona Health Sciences Center); UAZ08-11-01 (Other Identifier: DCP); P50CA095060 (U.S. NIH Grant/Contract); N01CN35158 (U.S. NIH Grant/Contract)