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Trial of a Gastrin Receptor Antagonist in Barrett's Esophagus

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. Identifier: NCT01298999
Recruitment Status : Active, not recruiting
First Posted : February 18, 2011
Last Update Posted : December 12, 2017
Trio Medicines Ltd.
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Julian A Abrams, MD, Columbia University

Brief Summary:
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 or disease Intervention/treatment Phase
Barrett's Esophagus Drug: YF476 Drug: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Randomized Placebo-Controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
Study Start Date : June 2010
Primary Completion Date : December 2017
Estimated Study Completion Date : June 2018

Arm Intervention/treatment
Experimental: YF476
YF476 (gastrin-receptor antagonist)
Drug: YF476
25 mg: one capsule to be taken by mouth once daily for 12 weeks.
Other Name: Netazepide
Placebo Comparator: Placebo
Placebo pill (identical in appearance to YF476 pills)
Drug: Placebo
Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
Other Name: No other name

Primary Outcome Measures :
  1. Change in Ki67 expression [ Time Frame: Up to 3 months from baseline ]
    The study is designed to examine decreases in tissue Ki67 expression, a marker of cellular proliferation.

Secondary Outcome Measures :
  1. Number of participants that experienced change in any biomarker expression [ Time Frame: Up to 3 months from baseline ]
    Biomarkers associated with esophageal adenocarcinoma, in particular, cyclooxygenase-2 (COX-2), p53, cholecystokinin 2 receptor (CCK2R) and doublecortin-like kinase 1 (DCAMKL1)

  2. Number of participants that experienced adverse events (any adverse events and/or severe adverse events) [ Time Frame: Up to 4 weeks after completion of study drug ]
    A measure of safety and tolerability

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Age >= 18 years, with histologically confirmed diagnosis of Barrett's Esophagus without dysplasia
  • Minimum of 1 cm circumferential Barrett's mucosa on endoscopy or at least 2 cm maximal contiguous extent of Barrett's mucosa
  • Proton pump inhibitor use at least once daily for at least twelve months prior to enrolment, and stable dose of PPI for the three months before enrolment
  • ECOG performance status ≤ 2 and Karnofsky ≥ 60%
  • Normal organ and marrow function
  • Use of adequate contraception during the study
  • Willingness to comply with all treatment and follow up procedures
  • Ability to understand and the willingness to sign a written informed consent document
  • Up to date with all age appropriate cancer screening tests, as per American Cancer Society guidelines

Exclusion Criteria:

  • Histologically confirmed BE with high grade dysplasia, invasive carcinoma of the esophagus, low grade dysplasia
  • Prior endoscopic therapy for BE
  • History of esophageal or gastric surgery
  • History of atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome
  • Participation in a trial of an investigational medicinal product within the previous 28 days
  • Prolonged QTc interval >450 msec
  • History of allergic reactions attributed to compounds of similar chemical composition to YF476
  • History of baseline findings of: diabetes mellitus requiring insulin therapy; pancreatitis; hepatitis B, hepatitis C or HIV; malabsorption syndrome or inability to swallow or retain oral medicine; major surgery ≤ 28 days prior to enrollment; ECOG performance status ≥ 2; or another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in situ; any clinically significant and uncontrolled major morbidity
  • Certain medicines and herbal remedies taken during the 7 days before the start of study drug
  • Has evidence of cancer at the time of enrolment, or has surveillance tests planned within 21 weeks after enrollment

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 identifier (NCT number): NCT01298999

United States, New York
New York Presbyterian Hospital - Columbia
New York, New York, United States, 10032
United Kingdom
National Institute for Health Research
Cambridge, United Kingdom
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

Responsible Party: Julian A Abrams, MD, Assistant Professor of Medicine, Columbia University Identifier: NCT01298999     History of Changes
Other Study ID Numbers: AAAE9648
YFBE-001 ( Other Identifier: Trio )
First Posted: February 18, 2011    Key Record Dates
Last Update Posted: December 12, 2017
Last Verified: December 2017

Keywords provided by Julian A Abrams, MD, 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
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs