Trial Outcomes & Findings for Clinical Studies on Bile Acids in Barrett's Esophagus (NCT NCT00858858)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

60 participants

Primary outcome timeframe

After 8 weeks of UDCA treatment

Results posted on

2015-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 Esophageal biopsy: After the esophageal perfusions described above, 12 biopsy specimens of the squamous epithelium will be taken at a level 2 cm proximal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses. In patients with Barrett's esophagus, 12 biopsy specimens of the specialized intestinal metaplasia also will be taken at a level 1 cm distal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.
Overall Study STARTED	60
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Studies on Bile Acids in Barrett's Esophagus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 n=42 Participants Esophageal biopsy: After the esophageal perfusions described above, 12 biopsy specimens of the squamous epithelium will be taken at a level 2 cm proximal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses. In patients with Barrett's esophagus, 12 biopsy specimens of the specialized intestinal metaplasia also will be taken at a level 1 cm distal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	37 Participants n=93 Participants
Age, Categorical >=65 years	5 Participants n=93 Participants
Sex: Female, Male Female	4 Participants n=93 Participants
Sex: Female, Male Male	38 Participants n=93 Participants
Region of Enrollment United States	42 participants n=93 Participants

PRIMARY outcome

Timeframe: After 8 weeks of UDCA treatment

Population: Patients with Barrett's esophagus, only metaplastic epithelium evaluated. No data were collected from squamous epithelium as originally planned because our in vitro studies subsequently showed that DCA exposure did not cause DNA damage in squamous cells and, therefore, oral UDCA treatment would be meaningless for squamous esophagus.

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.

Outcome measures

Outcome measures
Measure	Arm 1 n=21 Participants Esophageal biopsy: After the esophageal perfusions described above, 12 biopsy specimens of the squamous epithelium will be taken at a level 2 cm proximal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses. In patients with Barrett's esophagus, 12 biopsy specimens of the specialized intestinal metaplasia also will be taken at a level 1 cm distal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.
Protection Against DNA Damage by UDCA Before DCA Perfusion	1.068 Relative Densitometry Units Standard Error .17
Protection Against DNA Damage by UDCA After DCA Perfusion	.82 Relative Densitometry Units Standard Error .14

Adverse Events

Arm 1

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1 n=42 participants at risk Esophageal biopsy: After the esophageal perfusions described above, 12 biopsy specimens of the squamous epithelium will be taken at a level 2 cm proximal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses. In patients with Barrett's esophagus, 12 biopsy specimens of the specialized intestinal metaplasia also will be taken at a level 1 cm distal to the squamocolumnar junction at baseline (6 biopsies will be used to establish primary cell cultures and six will be used for molecular analyses); 6 more biopsy specimens will be taken at the same level immediately after bile acid perfusion for molecular analyses.
Vascular disorders Ruptured cerebral aneurysm	2.4% 1/42 • Number of events 1 • 3 years
Gastrointestinal disorders Ischemic colitis	2.4% 1/42 • Number of events 1 • 3 years
Cardiac disorders Death	2.4% 1/42 • Number of events 1 • 3 years
Gastrointestinal disorders Abdominal pain	2.4% 1/42 • Number of events 1 • 3 years

Other adverse events

Adverse event data not reported

Additional Information

Stuart Spechler

VA

Phone: 214-857-1603

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place