Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing

The efficacy of proton pump inhibitors (PPIs) is highly dependent on plasma concentrations
achieved following drug administration. All PPIs are metabolized in part by the CYP2C19
enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Depending on the CYP2C19
genotype, individuals are classified into different metabolizer phenotypes: poor metabolizers
(PM, 2 loss-of-function CYP2C19 alleles); intermediate metabolizers (IM, one loss-of-function
allele); normal metabolizers (NM, no loss or gain-of-function alleles); rapid metabolizer
(RM; one gain-of-function allele) and ultra-rapid metabolizers (UM, two gain-of
function-alleles). Genetic variants in CYP2C19 are known to profoundly influence PPI plasma
concentrations and consequently, response to PPI therapy. For example, individuals classified
as either RM or UM have lower PPI concentrations compared to NM or loss-of-function (LOF)
allele carriers, respond poorly to PPI therapy, and some fail to respond even when the PPI
dose is increased. The investigators hypothesize that genotype-supported PPI dosing will lead
to better GERD control and improvement in severity of dyspepsia symptoms compared to
conventional dosing. The investigators will conduct a comparative effectiveness study of
genotype-supported vs. conventional PPI dosing. Patients presenting with GERD or dyspepsia
symptoms and either 1) being initiated on PPI therapy or 2) with continued symptoms on
current PPI therapy will be recruited from gastroenterology clinics and randomized to a
genotype-supported versus conventional PPI therapy management strategy. The investigators
will integrate individual CYP2C19 genotype information into dosing decisions for the
genotype-supported arm and compare change in symptom control from baseline to the end of the
study between study arms. Given that PPI efficacy is related to PPI exposure and to
metabolizer phenotype, individualizing treatment using CYP2C19 genotype-supported dosing is
expected to improve symptom management. The investigators will also evaluate patient and
clinician knowledge and attitudes about pharmacogenetics testing and physician acceptance of
genetic information into clinical practice. Finally, the investigators will collect
preliminary data on the potential impact of CYP2C19-supported PPI dosing on adverse event
rates.

Inclusion Criteria:

- 18 years of age or older

- Gastroesophageal Reflux Disease symptoms

- Being initiated on PPI therapy OR continues to have symptoms despite PPI therapy

Exclusion Criteria:

- Extensive esophageal or gastric surgery

- Any chronic illness that would interfere with the study