Neuromodulators for Esophageal Disorders Related to Gut-Brain Interaction: Evaluating Tricyclic Antidepressants, SSRIs, and Proton Pump Inhibitors

What this Trial Is About

Gastroesophageal reflux disease (GERD) can be difficult to treat, especially for patients who do not respond to standard proton pump inhibitor (PPI) therapy. Many of these patients have esophageal disorders of gut-brain interaction (DGBI), including reflux hypersensitivity and functional heartburn. These conditions involve esophageal visceral hypersensitivity and hypervigilance, which cause symptoms without detectable structural or inflammatory damage. Diagnosing these disorders requires tests like endoscopy, pH-impedance monitoring, and high-resolution manometry. This study aims to evaluate how well neuromodulators work in managing esophageal DGBI and to explore differences in effectiveness among various neuromodulator types and esophageal DGBI subtypes. Participants will be randomly assigned to one of three groups for a 12-week treatment: tricyclic antidepressants (TCA) taken as 25 mg tablets twice daily, selective serotonin reuptake inhibitors (SSRI) taken as 50 mg tablets once daily, or proton pump inhibitors (PPI) taken as 30 mg orally dissolving tablets once daily. About 70 participants will be assigned to each group. Before starting treatment, participants will complete several questionnaires covering reflux symptoms, esophageal swallowing difficulties, anxiety, sleep quality, depression, and quality of life. At the end of the 12-week treatment period, participants will complete the same set of questionnaires again to assess changes in symptoms and quality of life. The questionnaires include the Gastroesophageal Reflux Disease Questionnaire, PROMIS GERD Questionnaire, Disease Symptom Index, Reflux Symptom Index, Brief Esophageal Dysphagia Questionnaire, Esophageal Hypervigilance and Anxiety Scale, Visceral Sensitivity Index, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, State-Trait Anxiety Inventory, Functional Dyspepsia Questionnaire, Irritable Bowel Syndrome Questionnaire, Short-Form-12 Health Survey, Northwest Esophageal Quality of Life Scale, and Global Symptom Severity Questionnaire. The study will provide insights into the effects of neuromodulators on esophageal DGBI and refractory GERD symptoms.

Neuroregulators for the Treatment of Diseases Associated With Esophageal-brain-gut Axis Communication Abnormalities.