Effectiveness of Physiologic Testing in PPI Non-Responders
Condition: Gastro Esophageal Reflux
MeSH terms: Gastroesophageal Reflux
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed description: 
      The prevalence of gastroesophageal reflux disease is estimated to be as high as 20% in the
      United States, and up to 50% of these patients remain symptomatic on proton pump inhibitor
      (PPI) therapy. Unfortunately, the clinical approach to understand the mechanism of
      nonresponse is not standardized, and patients will often undergo various esophageal function
      tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance
      manometry (HRIM), and 4) mucosal impedance. Currently significant 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. As such, PPINRs contribute to a large healthcare burden
      in the United States.

      The first aim of the study is to identify the relevant physiologic parameters of the
      aforementioned diagnostic tools in their ability to predict PPI requirement. Subsequently, 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.

      The investigators will first perform a prospective comparison trial of 240 PPINR subjects at
      two centers over a 4 year period. Subjects will complete symptom questionnaires and undergo
      diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hthe wireless pH monitoring off of
      PPI therapy and mucosal impedance). Those who have a positive pH study and/or resume PPI
      therapy will receive escalation of acid suppression therapy with dexlansoprazole. Experiments
      1a & 1b will compare the ability of 96-hthe wireless pH monitoring vs pH impedance to predict
      PPI requirement and response to dexlansoprazole, respectively. Experiment 1c will explore
      whether mucosal impedance is equivalent to 96-hthe wireless pH monitoring in predicting PPI
      requirement. Lastly, Experiment 1d 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 based
      on results from aim 1 in addition to the available literature & evidence. This will be
      conducted over twelve months (years 4 to 5).
    

Intervention name(s): dexlansoprazole
Intervention type(s): Drug
Intervention description(s): dexlansoprazole treatment for Gastroesophageal Reflux symptoms
Other intervention name(s): Dexilant
Intervention MeSH terms: Dexlansoprazole; Lansoprazole
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other