Clinical Studies on Bile Acids in Barrett's Esophagus

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ClinicalTrials.gov Identifier: NCT00858858

Recruitment Status : Completed

First Posted : March 10, 2009

Results First Posted : November 24, 2014

Last Update Posted : April 30, 2015

Sponsor:

Information provided by (Responsible Party):

VA Office of Research and Development ( US Department of Veterans Affairs )

Study Description

Brief Summary:

This study has two major goals:

To determine the effects of bile salts on causing DNA injury and activating signaling pathways that promote growth in cells from the esophagus of patients who have gastroesophageal reflux disease (GERD)
To determine whether changes in bile composition induced by treating patients with a bile salt called ursodeoxycholic acid (UDCA) can alter DNA injury, signaling pathway activation and other types of damage in cells from the esophagus of patients who have GERD.

Condition or disease	Intervention/treatment	Phase
Gastroesophageal Reflux Disease	Drug: Ursodeoxycholic Acid	Not Applicable

Show detailed description

Detailed Description:

Patients who have been scheduled for elective endoscopic examination at the Dallas VA Medical Center for the evaluation of GERD or Barrett's esophagus will be invited to participate in the study. Patients who provide written, informed consent will have a medical history taken.

Women of child bearing potential will have a pregnancy test. Eligible subjects will be treated with omeprazole 20 mg BID for at least four weeks before the scheduled endoscopic examination. Eight days before the endoscopy, patients will be instructed to discontinue any aspirin and other non-steroidal anti-inflammatory drugs (unless there is a contraindication to discontinuing those medications including a history of coronary artery disease, myocardial infarction, cerebrovascular accident or transient ischemic attacks). The endoscopic examination, which had been scheduled for clinical purposes, will be performed as usual, with biopsy specimens taken as required for clinical purposes.

When the clinical examination has been completed, a perfusion catheter will be passed through the biopsy channel and positioned 5 cm above the squamocolumnar junction in the distal esophagus. The distal esophagus will be perfused with 10cc of a 250 M solution of either deoxycholic acid (DCA) or ursodeoxycholic acid (UDCA) for 5 minutes. Odd-number patients enrolled in each of the two patient groups (GERD patients with and without Barrett's esophagus) will receive DCA, whereas even-number patients will receive UDCA. The catheter position, bile acid concentration and duration of bile acid perfusion are chosen to simulate a typical episode of gastroesophageal reflux.

In all patients, 12 biopsy specimens of the squamous epithelium will be taken using jumbo biopsy forceps at a level 2 cm proximal to the squamocolumnar junction at baseline (6 biopsies will be used to establish the primary cell cultures and six will be used for the molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.

In the patients with Barrett's esophagus, 12 biopsy specimens of the specialized intestinal metaplasia also will be taken using jumbo biopsy forceps at a level 1 cm distal to the squamocolumnar junction at baseline (6 biopsies will be used to establish the primary cell cultures and six will be used for the molecular analyses); 6 more biopsy specimens will be taken a t the same level immediately after bile acid perfusion for molecular analyses. All endoscopic procedures will be performed by Dr. S.J. Spechler.

All patients will be maintained on omeprazole 20 mg BID for one year, after which the endoscopic examinations will be repeated. The endoscopies will be performed with bile acid perfusions and biopsy sampling exactly as described above, except that patients who received DCA during the first examination will receive UDCA and vice-versa.

After the second endoscopy, patients will be treated with UDCA in a dose of 10 mg/kg for 8 weeks, after which a final endoscopy will be performed.

During this endoscopy, DCA perfusion will be performed as described above. In all patients, 6 biopsy specimens of the squamous epithelium will be taken using jumbo biopsy forceps at a level 2 cm proximal to the squamocolumnar junction at baseline for the molecular analyses; 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.

In the patients with Barrett's esophagus, 6 biopsy specimens of the specialized intestinal metaplasia also will be taken using jumbo biopsy forceps at a level 1 cm distal to the squamocolumnar junction at baseline for the molecular analyses; 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	60 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Clinical Studies on Bile Acids in Barrett's Esophagus
Study Start Date :	March 2009
Actual Primary Completion Date :	March 2013
Actual Study Completion Date :	February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: GERD

Drug Information available for: Ursodiol

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1 All patients are treated with DCA and UDCA perfusion of the esophagus, one year apart, followed by 8 weeks of treatment with oral ursodeoxycholic acid 10 mg/kg qd. Then a final DCA perfusion of the esophagus.	Drug: Ursodeoxycholic Acid 8 weeks of oral UDCA treatment 10 mg/kg qd Other Name: UDCA

Outcome Measures

Primary Outcome Measures :

Protection Against DNA Damage by UDCA [ Time Frame: After 8 weeks of UDCA treatment ]
p-H2AX levels are a measure of DNA damage. Our major outcome measure is the change in p-H2AX levels, expressed as relative densitometry units, after DCA perfusion in patients treated with oral UDCA. If UDCA protects against bile acid-induced DNA damage, then p-H2AX levels before and after perfusion should not change significantly.

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients who have been scheduled for elective endoscopic examination at the Dallas VA Medical Center for the evaluation of GERD or Barrett's esophagus

Exclusion Criteria:

Patients unwilling or unable to provide informed consent
Patients with esophageal carcinomas
Patients with esophageal varices
Patients taking warfarin or clopidogrel
Coagulopathy that precludes safe biopsy of the esophagus
Comorbidity that precludes safe participation in the study
Allergy to omeprazole or UDCA
Pregnancy

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00858858

Locations

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United States, Texas
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, United States, 75216

Sponsors and Collaborators

US Department of Veterans Affairs

Investigators

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Principal Investigator:	Stuart J Spechler, MD	VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

More Information

Publications:

Huo X, Juergens S, Zhang X, Rezaei D, Yu C, Strauch ED, Wang JY, Cheng E, Meyer F, Wang DH, Zhang Q, Spechler SJ, Souza RF. Deoxycholic acid causes DNA damage while inducing apoptotic resistance through NF-κB activation in benign Barrett's epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G278-86. doi: 10.1152/ajpgi.00092.2011. Epub 2011 Jun 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Peng S, Huo X, Rezaei D, Zhang Q, Zhang X, Yu C, Asanuma K, Cheng E, Pham TH, Wang DH, Chen M, Souza RF, Spechler SJ. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids. Am J Physiol Gastrointest Liver Physiol. 2014 Jul 15;307(2):G129-39. doi: 10.1152/ajpgi.00085.2014. Epub 2014 May 22.

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Responsible Party:	US Department of Veterans Affairs
ClinicalTrials.gov Identifier:	NCT00858858
Obsolete Identifiers:	NCT00849420
Other Study ID Numbers:	GAST-002-08F
First Posted:	March 10, 2009 Key Record Dates
Results First Posted:	November 24, 2014
Last Update Posted:	April 30, 2015
Last Verified:	April 2015

Additional relevant MeSH terms:

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Barrett Esophagus Gastroesophageal Reflux Esophageal Motility Disorders Deglutition Disorders Esophageal Diseases Gastrointestinal Diseases	Digestive System Diseases Precancerous Conditions Neoplasms Ursodeoxycholic Acid Cholagogues and Choleretics Gastrointestinal Agents

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