Thirty to 50 percent of patients diagnosed with gastroesophageal reflux disease (GERD) are not satisfied with symptom control derived from proton pump inhibitors (PPI). This group of patients;PPI non-responders (PPI- NR), pursue further diagnostic procedures and interventions with low yield. This approach is problematic because symptoms are not related to pathologic reflux in at least 50% of PPI-NRs referred for ambulatory reflux testing and therefore it does not lead to improved outcomes or even inform us as to why a patient did not respond to PPI. The development of novel therapies for this group is limited by lack of agreement on the definition of a PPI responder and the lack of a model that accounts for the heterogeneity of continued symptom generation. Our goal is to validate a PPI-NR model that accounts for factors above and beyond pathologic reflux, reducing the need for low-yield ambulatory reflux monitoring and informing the development of novel treatments. Study 1 will provide an equation in which pre-test clinical and questionnaire data sufficiently enables probability estimation for each of 4 reflux phenotypes, derived from ambulatory reflux monitoring. Study 2 will yield a similar equation which will predict one's ability to withdraw PPI therapy when indicated.

Public Health Relevance

Gastroesophageal reflux disease (GERD) is an increasingly common medical condition affecting at least ten percent of the adult US population. Despite the fact that proton pump inhibitors (PPI) are extremely effective, up to 30-50% of patients are unsatisfied with their response and continue to have refractory symptoms. This proposal seeks to identify the reason for continued symptoms and to determine whether a systematic diagnostic protocol will better define treatment strategies for PPI non-responders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK092217-02
Application #
8451889
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Hamilton, Frank A
Project Start
2012-04-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$324,277
Indirect Cost
$114,389
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Yadlapati, Rena; Tye, Michael; Keefer, Laurie et al. (2018) Psychosocial Distress and Quality of Life Impairment Are Associated With Symptom Severity in PPI Non-Responders With Normal Impedance-pH Profiles. Am J Gastroenterol 113:31-38
Stern, E K; Carlson, D A; Falmagne, S et al. (2018) Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients. Neurogastroenterol Motil 30:
Alexeeva, Olga; Keswani, Rajesh N; Pandolfino, John E et al. (2018) Electronic Clinical Decision Support Tools for Obesity and Gastroesophageal Reflux Disease: The Provider's Perspective. Am J Gastroenterol 113:916
Yadlapati, Rena; Pandolfino, John E; Alexeeva, Olga et al. (2018) The Reflux Improvement and Monitoring (TRIM) Program Is Associated With Symptom Improvement and Weight Reduction for Patients With Obesity and Gastroesophageal Reflux Disease. Am J Gastroenterol 113:23-30
Yadlapati, Rena; Tye, Michael; Roman, Sabine et al. (2018) Postprandial High-Resolution Impedance Manometry Identifies Mechanisms of Nonresponse to Proton Pump Inhibitors. Clin Gastroenterol Hepatol 16:211-218.e1
Carlson, D A; Kathpalia, P; Craft, J et al. (2018) The relationship between esophageal acid exposure and the esophageal response to volumetric distention. Neurogastroenterol Motil 30:
Yadlapati, Rena; Hungness, Eric S; Pandolfino, John E (2018) Complications of Antireflux Surgery. Am J Gastroenterol 113:1137-1147
Yadlapati, Rena; Craft, Jenna; Adkins, Christopher J et al. (2018) The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms. Clin Gastroenterol Hepatol 16:1670-1672
Hillman, L; Yadlapati, R; Thuluvath, A J et al. (2017) A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease. Dis Esophagus 30:1-15

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