Efficacy of Potassium-Competitive Acid Blockers in Barrett's Esophagus (PCAB BE Study)

This is a research study to look at how a new medication compares to standard treatment for reducing acid reflux in patients with Barrett's Esophagus. The study drug is Vonoprazan. This is a pill that is not yet FDA-approved for this purpose in this patient population. The participants will first continue their current acid-reducing medicine (PPI) once a day for at least 7 days. After that, they will have a test to measure acid levels in their esophagus (food tube) while still taking the PPI medication. After this test, they will stop their current PPI medication and start taking the study drug, Vonoprazan, once a day for 7-28 days. They will then have a second acid test while on the study drug (Vonoprazan). Before each test, the participants will complete a short questionnaire about their symptoms. The study team will collect their health history, including medical conditions and current medications. After they finish the study drug, they will have a follow-up visit in about 30 days. The participation in the study will then end.

Inclusion Criteria: * Adults aged 18 or older at time of consent. * Able to read and understand English and provide written informed consent. * History of Gastroesophageal Reflux Disease (GERD) with or without heartburn. * Diagnosed with nondysplastic Barrett's Esophagus (NBDE) defined as meeting the following within the past 3 years: * Endoscopically confirmed BE with segment length ≥2 cm (to avoid those with an irregular Z line), and * Histologic evidence of intestinal metaplasia without dysplasia ("dysplasia" includes indefinite for dysplasia). * Currently on proton pump inhibitor (PPI) maintenance therapy, defined as PPI prescribed once or twice daily for 3 or more months (defined as 90 days or more) from consent. Any formulation and dosage of PPI will be included, including pantoprazole, omeprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole or their generic equivalents. * If currently on twice daily PPI, then able to modify PPI regimen to once daily dosing as part of their routine clinical care. * Ability to take oral medication and willing to adhere to study intervention regimen. * Willing to follow lifestyle recommendations as outlined in protocol section 5.3 Exclusion Criteria: * Barrett's Esophagus (BE) with dysplasia (indefinite for dysplasia, or low-grade dysplasia, or high-grade dysplasia) diagnosed within 12 months of study entry. * Current or prior esophageal adenocarcinoma (EAC). * Use of other acid suppressive medications. * H. pylori diagnosis or treatment within the past 6 months prior to study entry. * History of upper gastrointestinal tract surgery (e.g., esophagectomy or surgery for reflux disease). * Current contraindication to 24hr pH impedance test, including: * Recent broken nose, nasal surgery, or known deviated septum; or * Bleeding disorders or those taking certain blood-thinning medications and unable to temporarily discontinue use per current clinical guidance may also be excluded due to increased risk of bleeding during catheter insertion; or * Individuals with implanted devices like pacemakers or defibrillators. * Known hypersensitivity or allergic reaction to any component of the study intervention. * Treatment with another investigational product within 30 days prior to consent. * Current use of rilpivirine-containing products. * Pregnant, breastfeeding, or considering becoming pregnant or intending to donate ova during the study and for 30 days after the last dose of study drug.