Genotype-tailored Treatment of Symptomatic Acid-Reflux in Children With Uncontrolled Asthma (GenARA)

  • STATUS
    Recruiting
  • days left to enroll
    25
  • participants needed
    110
  • sponsor
    Jason Lang, M.D., M.P.H.
Updated on 19 June 2022
corticosteroids
fluticasone
lansoprazole

Summary

This study will evaluate the effect of CYP2C19 and ABCB1 genes on pharmacokinetics of lansoprazole in children with mild gastroesophageal reflux (GER) and uncontrolled asthma. It will determine if genotype-guided lansoprazole dosing of lansoprazole improves GER and asthma control.

Description

BACKGROUND: Poorly controlled asthma especially in children remains a major public health problem. Many children with poor asthma control experience gastroesophageal reflux (GERD). The effect of mild GERD on asthma remains controversial despite studies involving proton-pump inhibitors (PPIs) assessing their effect on asthma. Past inconsistent findings regarding the effect of PPIs on asthma control may have resulted from ineffective dosing strategies of proton-pump inhibitors employed in these studies. Drug levels and efficacy vary widely in the population and depend on genetics. Dosing in children which adjusts for the gene CYP2C19 may improve efficacy and reduce side-effects leading to improved asthma control.

HYPOTHESIS: #1: The investigators hypothesize that genotype-tailored lansoprazole dosing will reduce asthma symptoms in children with mild symptoms of GERD compared to placebo. #2: CYP2C19 and ABCB1 genetic variants influence the pharmacokinetics (drug levels) of lansoprazole as determined by population pharmacokinetic modeling.

METHODS: The investigators will conduct a 6-month randomized controlled trial comparing genotype-tailored lansoprazole dosing versus matched placebo in the control of asthma symptoms in 6-17 year olds with asthma and mild reflux. All participants will have baseline pharmacokinetics analysis following a single genotype-tailored dose to assess the effects of CYP2C19 and ABCB1.

IMPACT: These results would be a major advance in the science of safe dosing of proton-pump inhibitors in children and for the management of the millions of children struggling with reflux and asthma.

Details
Condition Asthma, Gastroesophageal Reflux
Treatment Matched placebo, commercially available lansoprazole
Clinical Study IdentifierNCT03015610
SponsorJason Lang, M.D., M.P.H.
Last Modified on19 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age: 6-17 year olds with documented clinician-diagnosed asthma
Evidence of recent uncontrolled asthma (must meet at least one of the following). This convention for defining poorly-controlled asthma has been successfully used in a large pediatric trial
ACQ > 1.2
Use of short-acting beta-agonist for asthma symptoms twice/week or more on average over the past month
Nocturnal awakenings with asthma symptoms more than once per week on average over the last month
Two or more emergency department visits, unscheduled provider visits, prednisone courses or hospitalizations for asthma in the past 12 months
Currently on stable dose of daily inhaled corticosteroid medication (ICS) for asthma
control equivalent to 88mcg of fluticasone or greater for at least 6 weeks
Currently with mild GERD symptoms reported at V1 defined by a score on the Pediatric GERD Symptom Assessment Score greater than 15 and less than 80. GSAS ranges from 0 to >440
from the time of enrollment. Participant must be on National Asthma Education
and Prevention Program (NAEPP) controller step 2, 3 or 4

Exclusion Criteria

Taking daily CYP2C19 substrates, inducers or inhibitors medication
Past or current history of moderate-severe GERD or related disorders (erosive esophagitis, peptic ulcer disease, eosinophilic esophagitis) which in the opinion of the pediatric gastroenterology safety specialist/study physician requires treatment with acid-blocking agents
Daily use of a PPI for more than 4 consecutive weeks in the past 6 months
previous intubation for asthma
admission to intensive care unit for more than 24 hours for asthma in the past year
Previous surgery involving the esophagus or stomach (anti-reflux surgery, peptic ulcer surgery, trachea-esophageal fistula repair)
Forced expiratory volume in 1 second (FEV1) < 60% of predicted at enrollment
Any major chronic illness that would interfere with participation in the intervention or completion of the study procedures
History of phenylketonuria (PKU)
Medication use: treatment of GERD symptoms with over-the-counter antacids 4 days/week or more on average over past month
Theophylline preparations, azoles, anti-coagulants, insulin for Type 1 diabetes, digitalis, oral iron supplements when administered for iron deficiency within 1 month
Any investigational drugs within the past 2 months
Drug Allergies: previous allergic reaction from lansoprazole or other proton pump inhibitor medication or adverse reaction to aspartame
Inability to complete baseline measurements in a satisfactory manner according to the judgment of the research coordinator or site PI
Less than 75% completion of daily diary for asthma symptoms, SABA use and ICS medication adherence during the run-in period
Plan for family to move from study location within the next 6 months
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