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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01097304
First received: March 31, 2010
Last updated: July 22, 2014
Last verified: April 2014
  Purpose

This phase II trial studies how well ursodiol works in treating patients with Barrett esophagus or low-grade dysplasia. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ursodiol may in patients with Barrett esophagus or low-grade dysplasia.


Condition Intervention Phase
Barrett Esophagus
Esophageal Cancer
Drug: ursodiol
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Clinical Study of Ursodeoxycholic Acid in Barrett's Patients

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Reversal of oxidative DNA damage as assessed by changes in 8OHdG immunostaining [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Changes in percentage of positively stained nuclei in BE tissue sections from baseline to post-intervention [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in gastric bile acid composition, measured by liquid chromatography-tandem mass spectrometry, from baseline to post-intervention [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.

  • 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 [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.


Enrollment: 36
Study Start Date: April 2010
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ursodiol)
Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Drug: ursodiol
Given PO
Other Names:
  • Actigall
  • Deursil
  • UDCA
  • ursodeoxycholic acid
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 glutamic pyruvic transaminase [SGPT]) =< 2X 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01097304

Locations
United States, Arizona
Arizona Cancer Center - Tucson
Tucson, Arizona, United States, 85724-5024
Southern Arizona Veterans Affairs Health Center
Tucson, Arizona, United States, 85723
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
Investigators
Principal Investigator: Bhaskar Banerjee University of Arizona Health Sciences Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01097304     History of Changes
Other Study ID Numbers: NCI-2012-00450, NCI-2012-00450, CDR0000669111, 09-0141-03, UAZ08-11-01, P50CA095060, P30CA023074, N01CN35158
Study First Received: March 31, 2010
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Barrett Esophagus
Esophageal Neoplasms
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014