Genotype tailored treatment of mild symptomatic acid reflux in children with uncontrolled asthma (GenARA): Rationale and methods

Contemp Clin Trials. 2019 Mar:78:27-33. doi: 10.1016/j.cct.2019.01.009. Epub 2019 Jan 16.


Asthma causes enormous suffering and cost for children in the US and around the world [1-3]. Co-morbid gastroesophageal reflux disease (GERD) makes asthma management more difficult due to increased symptoms. Proton pump inhibitor (PPI) drugs are effective at improving to GERD symptoms, however they have demonstrated only modest and variable effects on asthma control in the setting of co-morbid GERD. Importantly, PPI metabolism and efficacy depend on CYP2C19 genotype. The Genotype Tailored Treatment of Symptomatic Acid Reflux in Children with Uncontrolled Asthma (GenARA) study is a randomized, double-blind, placebo-controlled trial to determine if genotype-tailored PPI dosing improves asthma symptoms among children with inadequately controlled asthma and GERD symptoms. This study has an innovative design to both assess the efficacy of genotype-tailored PPI dosing and perform pharmacokinetic modeling of the oral PPI Lansoprazole. Children ages 6-17 years old with clinician-diagnosed asthma and mild GERD symptoms will submit a saliva sample for CYP2C19 genotyping. Participants will undergo a two-step randomization to: (1) genotype-tailored versus conventional dosing of open-label oral lansoprazole for pharmacokinetic modeling, and (2) genotype-tailored lansoprazole daily versus placebo for 24 weeks to determine the effect of genotype-tailored PPI dosing on asthma control. Measures of asthma control, spirometry, and nasal washes during acute illnesses will be collected at 8-week intervals throughout the study. GenARA will better define the effects of CYP2C19 genotype on the dose response of lansoprazole in children and adolescents and assess if a novel dosing regimen improves GERD and asthma control.

Publication types

  • Clinical Trial Protocol
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / drug therapy
  • Asthma / epidemiology
  • Asthma / physiopathology*
  • Body Weights and Measures
  • Child
  • Cytochrome P-450 CYP2C19 / genetics
  • Double-Blind Method
  • Female
  • Gastroesophageal Reflux / drug therapy*
  • Gastroesophageal Reflux / epidemiology
  • Genotype
  • Humans
  • Lansoprazole / administration & dosage
  • Lansoprazole / adverse effects
  • Lansoprazole / pharmacokinetics*
  • Lansoprazole / therapeutic use*
  • Male
  • Models, Biological
  • Phenotype
  • Polymorphism, Genetic
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects
  • Proton Pump Inhibitors / pharmacokinetics*
  • Proton Pump Inhibitors / therapeutic use*
  • Research Design
  • Severity of Illness Index
  • Spirometry


  • Proton Pump Inhibitors
  • Lansoprazole
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19