CompletedEarly Phase 1

Effectiveness of Physiologic Testing in PPI Non-Responders

United States240 participantsStarted 2017-07-01

Plain-language summary

The prevalence of GERD is estimated to be as high as 20% in the US, and up to 50% remain symptomatic on proton pump inhibitor (PPI) therapy. The clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance (MI). Controversy exists regarding the best technique, optimal study protocol and treatment approach for the PPI non-responder (PPINR) group, resulting in inappropriate resource utilization and a failure to provide effective personalized care. The first aim is to identify the relevant physiologic parameters of diagnostic tools in their ability to predict PPI requirement. In Aim Two, these results will be applied to guide the formal development of a clinical algorithm for the management of PPINRs with personalized clinical pathways based on mechanism of treatment failure. We will first perform a prospective comparison trial of 240 PPINR subjects at 2 sites over 4 years. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hr wireless pH monitoring off PPI therapy and MI). Those who have a positive pH study and/or resume PPI therapy will receive escalation of therapy with dexlansoprazole. We will compare the ability of 96-hr wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. We will explore whether MI is equivalent to 96-hr wireless pH monitoring in predicting PPI requirement. Lastly, we will determine whether HRIM metrics can be utilized to determine reflux burden, mechanism and response to treatment. Next, the investigators will develop quality measures for reflux testing in order to develop a simplified management strategy for the PPINR group. The RAND/UCLA Appropriateness Methodology will be utilized with an expert working group to develop formal validated quality measures for reflux testing.

Who can participate

Age range18 Years – 80 Years

SexALL

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Inclusion Criteria: * Male or female subjects aged 18-80 years old (females of childbearing potential should be on highly effective contraceptive methods) * Mentally capable to provide informed consent in English * Present to the Northwestern Medical Group GI practice or the Washington University Division of Gastroenterology with symptoms of GERD (heartburn, regurgitation, and non-cardiac chest pain) * Have failed an appropriate compliant trial of PPI therapy with a GERD-Q score ≥8. * Able to undergo endoscopy, ambulatory reflux monitoring, manometry, PPI therapy cessation and trial of dexlansoprazole therapy. Subjects with Los Angeles Classification Grade A (mild) or B esophagitis and symptomatic, non-erosive disease will be enrolled. 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) * Eosinophilic esophagitis * Prior gastrointestinal surgery of the esophagus and/or stomach * Current treatment with dexlansoprazole * 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. * Subjects with clinically abnormal results of the screening ECG and/or chemistry panel (particularly prolonged QTc interval or hypomagnesaemia) excluded from the dexlansoprazole tri…

What they're measuring

number of patients able to successfully withdraw from PPI treatment

Timeframe: 4.5 years

Trial details

NCT IDNCT03202537

SponsorNorthwestern University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2022-07-31