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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01097304
Recruitment Status : Completed
First Posted : April 1, 2010
Results First Posted : May 15, 2015
Last Update Posted : December 19, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE March 31, 2010
First Posted Date  ICMJE April 1, 2010
Results First Submitted Date  ICMJE April 29, 2015
Results First Posted Date  ICMJE May 15, 2015
Last Update Posted Date December 19, 2017
Study Start Date  ICMJE April 2010
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2014)
Reversal of Oxidative DNA Damage as Assessed by Changes in 8-hydroxy-2' -Deoxyguanosine (8OHdG) Immunostaining [ Time Frame: Baseline to 6 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
Reversal of oxidative DNA damage
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2017)
  • 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and 6 months ]
    Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 31, 2010)
  • Changes in gastric bile acid composition
  • Changes in cell proliferation in LGD BE epithelium
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ursodiol in Treating Patients With Barrett Esophagus and Low-Grade Dysplasia
Official Title  ICMJE Clinical Study of Ursodeoxycholic Acid in Barrett's Patients
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Barrett Esophagus
  • Esophageal Carcinoma
Intervention  ICMJE
  • Drug: Ursodiol
    Given PO
    Other Names:
    • Actigall
    • Deursil
    • UDCA
    • URSO
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE Experimental: Treatment (ursodiol)
Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Ursodiol
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2010)
36
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01097304
Other Study ID Numbers  ICMJE NCI-2012-00450
NCI-2012-00450 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
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 )
P30CA023074 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bhaskar Banerjee University of Arizona Health Sciences Center
PRS Account National Cancer Institute (NCI)
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP