Effectiveness of Physiologic Testing in PPI Non-Responders
Status:
Enrolling by invitation
Trial end date:
2022-03-31
Target enrollment:
Participant gender:
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.
Phase:
Early Phase 1
Details
Lead Sponsor:
Northwestern University
Collaborators:
Vanderbilt University Washington University School of Medicine