Targeting Hypervigilance and Autonomic Arousal: the Psycho-physiologic Model of Gastroesophageal Reflux Disease (GERD)

GERD affects roughly 20% of the U.S. population and the direct and indirect costs of GERD are substantial, totaling close to 50 billion dollars per year. Evidence supports that a large proportion of this cost and poor clinical outcomes in GERD are related to poor healthcare decisions by both the physician and the patient. The problem of inappropriate GERD management stems from three main issues. First, the disease is heterogeneous and requires treatment informed by a precision model. Second, the current paradigm largely ignores the important brain-gut interactions that drive symptoms and healthcare utilization. Third, there is a paucity of well-performed comparative effectiveness trials focused on assessing treatments beyond acid suppression. We will use physiomarkers defined during the previous funding cycle to phenotype the patients and use cognitive behavioral interventions to modulate hypervigilance to test the Psycho-Physiologic Model of GERD. Cognitive Behavioral Therapy (CBT) is able to improve hypervigilance and symptom specific autonomic arousal and thus, we will test our theory that CBT can improve outcomes in GERD by targeting these two important psychologic stressors. We will also continue our focus on the interplay of psychology and physiology by determining whether increased mucosal permeability is associated with reflux perception and whether this is modified by hypervigilance and autonomic disruption.

Inclusion Criteria: * Male or female subjects (females of childbearing potential should be on highly effective contraceptive methods) * Aged 18-80 years old * Mentally capable to provide informed consent * Fluent in English * Have symptoms of GERD (heartburn, regurgitation, and non-cardiac chest pain) * Have failed an appropriate compliant trial of PPI therapy with a GERDQ score ≥6. * Able to undergo endoscopy, ambulatory reflux monitoring, and manometry * Be interested in behavioral interventions for ongoing symptoms. Exclusion Criteria: * Participation in a concurrent clinical trial or completed another trial within past 8 weeks. * Active severe erosive esophagitis (Los Angeles Grade C or D), Long segment Barrett's esophagus (Zap score of 4) * Prior gastrointestinal surgery of the esophagus and/or stomach * Current signs or symptoms of heart disease. All patients with non-cardiac chest pain are required to have a cardiologist evaluation as standard of care work up in the evaluation of non-cardiac chest pain. * Unstable medical illness with ongoing diagnostic work-up and treatment. Patients with well-controlled hypertension, diabetes and a remote history of ischemic heart disease that is deemed stable, as judged by the investigator can be included. * History of drug addiction, drug abuse or alcoholism. * Current neurologic or cognitive impairment, which would preclude ability to obtain informed consent. * Pregnant patients. * Special vulnerable populations including children, prisoners, institutionalized individuals. * Bleeding disorder or requirement of NSAID/aspirin during monitoring period. * Drugs that affect gastrointestinal symptoms (H2 blockers, antacids, metoclopramide, domperidone, erythromycin, anticholinergics \[bentyl, levsin, belladonna etc.\]). Antidepressants can be continued at stable dose. * Patients found to have achalasia, a spastic disorder, hypercontractile disorder or functional obstruction at the esophagogastric junction will be excluded