Implementation of PPI Medication PGX Testing
Condition: Gastroesophageal Reflux
MeSH terms: Gastroesophageal Reflux
Study type: Interventional
Phase: Phase 4

Summary: 
      Using genetic information about the individual to pick the right drug for the right disease
      at the right dose defines personalized medicine. This pilot study seeks to institute
      pharmacogenomic testing, that is identifying genetic variation that influences patient
      response to drugs, into the Nemours Children's Health system. We propose to initiate the
      study by identifying genetic differences in cyp2c19, a gene that is responsible for a certain
      enzyme in the liver that metabolizes many drugs including a class of drugs called proton pump
      inhibitors (ppi; Prevacid, Nexium). PPIs are used to treat heartburn and other symptoms of
      gastroesophageal reflux disease (gerd) and are extensively used in pediatrics. Chronic use of
      PPIs can cause serious side effects including cold, pneumonia and stomach infections, which
      gets worse at higher doses. Children who poorly metabolize drugs because of genetic variation
      in cyp2c19 should get lower doses of PPIs than children who metabolize PPIs normally. Our
      pilot study will genotype children with gerd or other stomach acid mediated conditions for
      which a PPI is prescribed using a sample of spit to determine which dose of PPI they get
      based on the form of the cyp2c19 gene they have. We will study 120 children 2-17 yo diagnosed
      with gastroesophageal reflux disease (gerd) or other stomach acid mediated conditions for
      which a ppi is prescribed . Genetic results are available in < 60 minutes, and their doses
      are determined by their doctor based on genetic results. This study will allow us to gain
      valuable experience that will be used to expand our genetic program to other genes and drugs.
    

Detailed description: 
      The long-term objective of this research is to implement pharmacogenomic (PGX) testing of
      approved gene-drug pairs to maximize the efficacy and minimize adverse events for drugs that
      are used to treat childhood disease. Personalized medicine, that is, the use of the patient's
      own genetic information to predict the right dose of the right drug, has been a goal of
      medicine's since the publication of the human genome and HAPMAP projects. However, the
      adoption of PGX testing has been slow owing to several barriers and challenges. Recently
      President Obama announced the precision medicine initiative, which includes PGX testing, and
      has earmarked $ 1 b to implement it. The precision medicine initiative is expected to move
      personalized medicine forward so that most patients including pediatric patients will
      benefit. The Nemours Children's Health System is uniquely positioned to lead the effort to
      personalize medicine among pediatric patients. The goal of the proposed 1-year pilot project
      is to implement PGX testing in the Nemours children's health system. The experience,
      knowledge and skills gained in this pilot project will position Nemours to help lead
      precision medicine initiatives including PGX testing among pediatric populations. To
      implement PGX testing in Nemours we propose to begin testing the cyp2c19 - proton pump
      inhibitor gene-drug pair in the division of gastroenterology, Nemours children's hospital. A
      total of 120 children 2-17 yo who have been diagnosed with gastroesophageal reflux disease
      (GERD) or other stomach acid mediated conditions for which a PPI is prescribed will be
      recruited into the study by pediatric gastroenterologists (aim 1a). Drs. Franciosi and Lima
      will educate staff in the division of PGX testing and of the study. GI pediatricians are not
      required to participate in PGX testing. After obtaining consent, the study coordinator will
      obtain and bar code samples of saliva from the patient. Samples will be genotyped by Spartan
      Rx, a point-of-care genotyping platform, which are housed (2 of them) in the division of
      pathology. Loss-of-function alleles (*2, *3) and the gain-of-function allele (*17) are
      identified in < 60 minutes. The result of genotyping will be checked by dr. Badizadegan and
      entered into the patient's EMR. Clinical Decision Support (CDS) tools will advise Drs.
      Badizadegan and Franciosi of the patient's metabolic phenotype based on cyp2c19 genotype. Dr.
      Franciosi (or other GI pediatricians) will decide the dose of PPI to use based CDS tools
      carrying algorithms for conventional dosing and for genotype-guided dosing of PPIs. The
      electronic prescription for the PPI with genotype-guided dosing will be called in. PPI
      efficacy and safety for each study participant will be monitored weekly (aim 1B) by
      collecting and recording scores on validated GERD and adverse reaction questionnaires.
      Efficacy and safety scores will be communicated by each participant (or caregiver) using
      mobile devices (iPhone; computer) and recorded using redcap. Dr. Blake will supervise this
      phase of the study. Outcome metrics for aim 1A include: % of patients agreeing to volunteer
      for the study; % of patients reporting efficacy and toxicity data; % of providers agreeing to
      participate in study; and % of participants agreeing to future use of DNA. Outcome metrics
      for aim B will be judgments by Dr. Franciosi and his staff regarding success based on scores
      from GERD and adverse event questionnaires.
    

Intervention name(s): Genotype Guided PPI Dosing
Intervention type(s): Drug
Intervention description(s): Dosing of PPIs such as Prevacid and Nexium will be recommended based on CYP2C19 genotype information.
Other intervention name(s): Prilosec; Nexium; Prevacid; Proton Pump Inhibitor
Intervention MeSH terms: Proton Pump Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment