Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Columbia University
Trio Medicines Ltd.
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Julian A Abrams, MD, Columbia University Identifier:
First received: February 14, 2011
Last updated: October 15, 2015
Last verified: October 2015
The purpose of this study is to determine whether treatment with an experimental drug called YF476 in patients with Barrett's esophagus reduces the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.

Condition Intervention Phase
Barrett's Esophagus
Drug: YF476
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Cellular proliferation [ Time Frame: Up to 3 months from baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in biomarker expression [ Time Frame: Up to 3 months from baseline ] [ Designated as safety issue: No ]
  • Number of participants with adverse events (any adverse events and/or severe adverse events) as a measure of safety and tolerability. [ Time Frame: Up to 4 weeks after completion of study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 22
Study Start Date: November 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: YF476
YF476 (gastrin-receptor antagonist)
Drug: YF476
Subjects will take YF476, 25 mg capsules, once daily, for three months.
Other Name: Netazepide
Placebo Comparator: Placebo
Placebo pill (identical in appearance to YF476 pills)
Drug: Placebo
Subjects will take placebo pill (identical in appearance to YF476 pills) once daily for 3 months.

Detailed Description:
The association between gastro-esophageal reflux disease (GERD) and cancer of the esophagus is well-established. Barrett's esophagus (BE) is a condition in which the lining of the part of the esophagus changes to look like small intestine, and this change occurs in the setting of GERD. Patients with BE are at increased risk for developing esophageal cancer. It is recommended that all patients with BE take medicines called proton pump inhibitors (PPIs), which greatly reduce the acid produced by the stomach, in the hopes of reducing the risk of esophageal cancer. However, by reducing the acid level in the stomach, levels of a hormone called gastrin are increased. There is laboratory data to suggest that gastrin may have effects that actually promote the development of cancer, including esophageal cancer. The investigators previously showed that BE patients with very high gastrin levels are more likely to have either advanced precancerous changes (also called high grade dysplasia) or cancer of the esophagus. As such, the obvious question is raised: does gastrin promote the development of cancer in BE? YF476 is a new drug that blocks the effects of gastrin. Trials in healthy subjects have demonstrated that the drug is safe and well-tolerated. The investigators therefore propose to conduct a randomized placebo-controlled trial of YF476 in patients with Barrett's esophagus. The primary hypothesis is that treatment with YF476 will reduce the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed diagnosis of Barrett's esophagus
  • Ability to tolerate PPIs
  • Age >18

Exclusion Criteria:

  • History of histologically confirmed BE with LGD, HGD, or EAC
  • History of endoscopic therapy for BE
  • History of atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome
  • Any history of esophageal or gastric surgery
  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 identifier: NCT01298999

Contact: Adriana Rodriguez,CCRP 212-304-5606

United States, New York
New York Presbyterian Hospital - Columbia Recruiting
New York, New York, United States, 10032
Contact: Adriana Rodriguez,CCRP    212-304-5606   
United Kingdom
National Institute for Health Research Recruiting
Cambridge, United Kingdom
Contact: Rebecca Fitzgerald   
Contact: Rachel de la Rue    01223 348270 ext 58270   
Sponsors and Collaborators
Julian A Abrams, MD
Trio Medicines Ltd.
National Institute for Health Research, United Kingdom
Principal Investigator: Julian A Abrams, MD, MS Columbia University
  More Information

Responsible Party: Julian A Abrams, MD, Assistant Professor of Medicine, Columbia University Identifier: NCT01298999     History of Changes
Other Study ID Numbers: AAAE9648  YFBE-001 
Study First Received: February 14, 2011
Last Updated: October 15, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Barrett's esophagus
Esophageal adenocarcinoma
Acid Reflux

Additional relevant MeSH terms:
Barrett Esophagus
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases processed this record on May 26, 2016