Trial Information

The Effect of Proton Pump Inhibitors on Transmucosal Esophageal Leak

In a related study, we have found evidence that patients with Barrett's esophagus have a
leak for oral sucrose to leave the lumen of their upper gastrointestinal tract, enter the
blood, and be filtered into urine. Normally the disaccharide sucrose cannot leave the lumen
of the gastrointestinal tract without being first hydrolyzed to glucose and fructose.
Appearance of the disaccharide in the bloodstream suggests a paracellular leak of some type
in the upper gastrointestinal tract. Once in the blood, sucrose is likewise not taken up or
metabolized by the kidney but simply filtered into the urine. The amount of sucrose
appearing in an overnight urine sample can be used to indicate the presence of Barrett's
esophagus and/or esophagitis in a patient reporting with reflux (GERD) symptoms. The leak
is presumably in the Barrett's epithelium itself. This phenomenon will be used to test if a
standard 8 week therapy of Nexium in a first-time-presenting GERD patient can reduce the
leak as a means of assessing the efficacy of the drug in that patient. We predict that
Nexium will reduce leak in esophagitis but not Barrett's patients.

In this study, patients over 18 years of age presenting with GERD symptoms to a primary care
physician, will be recruited after providing informed consent. Patients will perform a
sucrose leak test the evening after their recruitment by drinking a solution of 100 gms of
sucrose in 200 cc of water at bedtime, then collecting an overnight urine sample (8 hrs).
Within 5 days the patient will undergo an upper endoscopy exam. The patient will then begin
Nexium therapy (40 mg/day of Esomeprazole) for 8 weeks, taking the dose each morning before
breakfast. After 8 weeks the patient will undergo a second sucrose leak test as described
above. Urine sucrose will be determined by HPLC.