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

• 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: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Barrett Esophagus; Esophageal Carcinoma
• Interventions: Drug: Ursodiol; Other: Laboratory Biomarker Analysis
• Enrollment: 36

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description	Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
Started	36
Completed	29
Not Completed	7

Baseline Characteristics

Arm/Group Title		Treatment (Ursodiol)
Arm/Group Description		Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Number of Baseline Participants		36
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	20 55.6%
	>=65 years	16 44.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	36 participants
		62.8 (10.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	36 participants
	Female	6 16.7%
	Male	30 83.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	36 participants
		36

Outcome Measures

1. Primary Outcome

Title	Reversal of Oxidative DNA Damage as Assessed by Changes in 8-hydroxy-2' -Deoxyguanosine (8OHdG) Immunostaining
Description	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.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

participants with fewer than 500 total nuclei in longitudinally sectioned crypts opening to the lumen were excluded from analysis

Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description:	Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: % of strongly/moderately stained nuclei
	1.62 (13.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ursodiol)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.54
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

2. Secondary Outcome

Title	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
Description	[Not Specified]
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

analysis was limited to participants with baseline and 6-month gastric fluid

Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description:	Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	28
Median (Inter-Quartile Range); Unit of Measure: % of total bile acid
	66.28; (36.29 to 77.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ursodiol)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	signed rank test
	Comments	[Not Specified]

3. Secondary Outcome

Title	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
Description	[Not Specified]
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

analysis was limited to participants with baseline and 6-month gastric fluid

Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description:	Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	28
Median (Inter-Quartile Range); Unit of Measure: % of total bile acid
	-13.31; (-46.98 to 0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ursodiol)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.01
	Comments	[Not Specified]
	Method	signed rank test
	Comments	[Not Specified]

4. Secondary Outcome

Title	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
Description	Results will be analyzed using paired t-tests. Results (mean values and changes during intervention) will be reported along with the corresponding confidence intervals.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

tissue slides with fewer than 500 total nuclei in longitudinally sectioned crypts opening to the lumen were excluded from analysis

Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description:	Patients receive ursodiol PO (13 to 15 mg/kg/day) BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Number of Participants Analyzed	29
Mean (Standard Deviation); Unit of Measure: % change
	1.36 (13.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Ursodiol)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.48
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Ursodiol)
Arm/Group Description	Patients receive ursodiol PO BID for 6 months in the absence of disease progression or unacceptable toxicity. Ursodiol: Given PO Laboratory Biomarker Analysis: Correlative studies
All-Cause Mortality
	Treatment (Ursodiol)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Treatment (Ursodiol)
	Affected / at Risk (%)
Total	5/36 (13.89%)
Cardiac disorders
Hypotension	1/36 (2.78%)
Ischemia/Infarction	1/36 (2.78%)
Atrial Fibrillation	1/36 (2.78%)
Chest/Thorax pain	1/36 (2.78%)
Gastrointestinal disorders
Enteritis	1/36 (2.78%)
Barrett's esophagus with at least intramucosal carcinoma	1/36 (2.78%)
Pancreatitis	1/36 (2.78%)
Musculoskeletal and connective tissue disorders
Post surgical pain	1/36 (2.78%)
Nervous system disorders
CNS cerebrovascular ischemia	1/36 (2.78%)
Altered mental status	1/36 (2.78%)
Renal and urinary disorders
Renal failure	1/36 (2.78%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment (Ursodiol)
	Affected / at Risk (%)
Total	31/36 (86.11%)
Cardiac disorders
hypertension	2/36 (5.56%)
Gastrointestinal disorders
Colitis	2/36 (5.56%)
Constipation	4/36 (11.11%)
Diarrhea	10/36 (27.78%)
Distention/Bloating	2/36 (5.56%)
Flatulence	2/36 (5.56%)
Heartburn	3/36 (8.33%)
Nausea	7/36 (19.44%)
Phytobezoar	2/36 (5.56%)
Vomiting	6/36 (16.67%)
Abdomen pain	4/36 (11.11%)
Stomach pain	3/36 (8.33%)
General disorders
Fatigue	4/36 (11.11%)
Fever	2/36 (5.56%)
Infections and infestations
Upper airway infection	6/36 (16.67%)
Investigations
Weight loss	2/36 (5.56%)
Metabolism and nutrition disorders
Hyponatremia	2/36 (5.56%)
Musculoskeletal and connective tissue disorders
Back pain	3/36 (8.33%)
Joint pain	3/36 (8.33%)
Nervous system disorders
Dizziness	6/36 (16.67%)
Headache	6/36 (16.67%)
Skin and subcutaneous tissue disorders
Pruritus	2/36 (5.56%)
Rash	3/36 (8.33%)
Vascular disorders
Phlebitis	2/36 (5.56%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Sherry Chow
• Organization: University of Arizona
• Phone: 520-626-3358
• EMail: schow@azcc.arizona.edu

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01097304
• Other Study ID Numbers: 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 )
• First Submitted: March 31, 2010
• First Posted: April 1, 2010
• Results First Submitted: April 29, 2015
• Results First Posted: May 15, 2015
• Last Update Posted: December 19, 2017