Genotype-tailored Treatment of Symptomatic Acid-Reflux in Children With Uncontrolled Asthma (GenARA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03015610|
Recruitment Status : Recruiting
First Posted : January 10, 2017
Last Update Posted : May 31, 2022
|Condition or disease||Intervention/treatment||Phase|
|Asthma Gastroesophageal Reflux||Drug: commercially available lansoprazole Drug: matched placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Genotype-tailored Treatment of Symptomatic Acid-Reflux in Children With Uncontrolled Asthma|
|Actual Study Start Date :||October 31, 2017|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Placebo Comparator: Placebo
participants will receive oral blinded matched placebo once daily
Drug: matched placebo
these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily placebo for 24 weeks
Other Name: once daily
Experimental: Genotype-guided Lansoprazole
participants will receive oral blinded commercially available lansoprazole once daily with a dose appropriate for the participant's metabolizer phenotype
Drug: commercially available lansoprazole
these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily lansoprazole for 24 weeks
Other Name: once daily
- Change in Asthma Control Questionnaire (ACQ) from Screening through Week 26 [ Time Frame: Measured at weeks -2 (screening), 0 (baseline), 8, 16, 26 ]The ACQ considers a broad set of common indicators of asthma control including use of bronchodilators, cough, nocturnal symptoms, level of activity, and pulmonary function.
- Change in GERD Symptom Assessment Questionnaire Score (GSAS) from Screening through Week 26 [ Time Frame: Measured at weeks -2 (screening), 0 (baseline), 4, 8, 12,16, 20, 26 ]A 10-item tool that has been validated in children in the assessment of gastroesophageal reflux disease related symptoms such as chest/abdominal pain, pain/choking with eating, swallowing dysfunction, regurgitation and nausea. It assesses symptom frequency and severity from the previous 7-days on an 8-point scale with 0 and 7 indicating the least and greatest severity, respectively.
- Change in Asthma Symptom Utility Index (ASUI) from Screening through Week 26 [ Time Frame: Measured at weeks -2 (screening), 0 (baseline), 8, 16, 26 ]Questionnaire measures changes in asthma control.
- Annualized rate of asthma exacerbations [ Time Frame: Week 0 (baseline) through Week 26 ]An exacerbation will be defined per the recommendations of the NIH Asthma Exacerbation Taskforce and will be defined as a worsening of asthma requiring the use of a systemic corticosteroid (at least 3 days of prednisolone/ prednisone or ≥1 days of dexamethasone) to prevent asthma worsening.
- Annualized rate of Episodes of Poor Asthma Control (EPAC) [ Time Frame: Week 0 (baseline) through Week 26 ]A study EPAC will be present if the participant meets any of the following criteria, (1) addition of systemic corticosteroid medication for asthma as above, (2) any unscheduled visit to a non-study related health care provider (ED, urgent care, hospital) for asthma symptoms, (3) increased use of rescue Short-Acting Beta Agonists (SABA) by more than 4 additional puffs (or more than 2 additional nebulizations) above baseline amount determined at enrollment.
- Annualized rate of respiratory tract infection (RTI) [ Time Frame: Week 0 (baseline) through Week 26 ]Participants/Caregivers will be asked to document symptoms of RTI on daily diary cards per consensus definitions. RTI symptoms will include: (1) runny nose; (2) stuffy or blocked nose or noisy breathing; (3) cough; (4) fever, feels hot, or has chills; (5) sore throat; and (6) sneezing.
- Change in Lung Function Testing from Screening through Week 26 [ Time Frame: Measured at week -2 (screening), week 26 ]Forced Expiratory Volume in 1 Second (FEV1) measurement
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03015610
|Contact: Joan Wilson, BSNfirstname.lastname@example.org|
|United States, Florida|
|Nemours Children's Specialty Care||Recruiting|
|Jacksonville, Florida, United States, 32207|
|Contact: Kathryn Blake, Pharm.D. 904-697-3806 ext 55-3806 email@example.com|
|Principal Investigator: Kathryn Blake, Pharm.D.|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Joan Wilson, BSN 919-681-8739 firstname.lastname@example.org|
|Principal Investigator: Jason E Lang, MD, MPH|
|Principal Investigator:||Jason E Lang, MD, MPH||Duke Health|