AsthmaPhase 3GenARANCT03015610
Genotype-tailored Treatment of Symptomatic Acid-Reflux in Children With Uncontrolled Asthma
A Phase 3 study testing commercially available lansoprazole in people with Asthma and Gastroesophageal Reflux, run by Jason Lang, M.D., M.P.H. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 17 years
- Conditions the study is for
- Asthma, Gastroesophageal Reflux
- What is being tested?
- commercially available lansoprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 41 participants
- Where
- 2 sitesUnited States
- Study dates
- 31 Oct 2017to 18 Jan 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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 from the time of enrollment. Participant must be on National Asthma Education and Prevention Program (NAEPP) controller step 2, 3 or 4.
- 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.
Who cannot join
- 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);
Show all 16Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University Medical Center
Durham, North Carolina, 27710
Nemours Children's Specialty Care
Jacksonville, Florida, 32207
About this study
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.
Read the detailed 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.
- Conditions
- Asthma, Gastroesophageal Reflux
- Being tested
- commercially available lansoprazole, matched placebo
- Keywords
- Personalized Medicine, CYP2C19, Lansoprazole, Pharmacokinetics
- Medical subject headings
- Asthma, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
commercially available lansoprazoleDrug
Also called once daily
these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily lansoprazole for 24 weeks
matched placeboDrug
Also called once daily
these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily placebo for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | participants will receive oral blinded matched placebo once daily Receives: Drug: matched placebo |
| Genotype-guided Lansoprazole | Experimental | participants will receive oral blinded commercially available lansoprazole once daily with a dose appropriate for the participant's metabolizer phenotype Receives: Drug: commercially available lansoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Asthma Control Questionnaire (ACQ) From Screening Through Week 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. Scores range between 0 (totally controlled) and 6 (severely uncontrolled). Reported is the change from week 0 to week 26; a negative change value indicates an improvement in asthma control.
Measured: Week 0 (baseline) to week 26
Secondary outcomes (6)
Change in GERD (Gastroesophageal Reflux Disease) Symptom Assessment Questionnaire Score (GSAS) From Screening Through Week 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. The total score ranges from 0 to 70, where a higher score indicates greater GERD symptom severity. Reported is the change from week 0 to week 26.
Measured: Week 0 (baseline) to week 26
Change in Asthma Symptom Utility Index (ASUI) From Screening Through Week 26
Questionnaire measures changes in asthma control. Each of the 11 items are scored on a 4-point Likert scale to assess frequency (not at all, 1 to 3 days, 4 to 7 days, and 8 to 14 days) and severity (not applicable, mild, moderate, and severe). The adjusted overall score ranges from 0 (worst possible symptoms) to 1 (no symptoms). Reported is the change from week 0 to week 26.
Measured: Week 0 (baseline) to week 26
Annualized Rate of Asthma Exacerbations
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.
Measured: Up to week 26
Annualized Rate of Episodes of Poor Asthma Control (EPAC)
A study EPAC will be present if the participant meets any of the following criteria, (1) addition of systemic corticosteroid medication for asthma or (2) any unscheduled encounter to a non-study related health care provider (phone contact, ED, urgent care, hospital) for asthma symptoms.
Measured: Up to week 26
Annualized Rate of Respiratory Tract Infection (RTI)
Participants/Caregivers will be asked to report diagnoses of RTI that occurred during the treatment period using interval reporting. RTI will include: (1) bronchitis, (2) otitis, (3) pneumonia.
Measured: Up to week 26
Change in Lung Function Testing From Screening Through Week 26
Forced Expiratory Volume in 1 Second (FEV1) measurement (mean change in FEV1 percent predicted from screening).
Measured: Week -2 (screening) to week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2017 (estimated)
- Study start31 Oct 2017
- Primary completion18 Jan 2024
- Study completion18 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jason Lang, M.D., M.P.H.
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund, Nemours Children's Clinic
- Responsible party
- Sponsor-investigator, Jason Lang, M.D., M.P.H., Duke University
- Investigators
- Jason E Lang, MD, MPH, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03015610
- Sponsor's protocol ID
- Pro00079073
- Acronym
- GenARA
- Status last verified
- Aug 2025
- First submitted
- 13 Dec 2016
- Last updated
- 9 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype-tailored Treatment of Symptomatic Acid-Reflux in Children With Uncontrolled Asthma
- ClinicalTrials.gov ID
- NCT03015610
- Acronym / sponsor ID
- GenARA / Pro00079073
- Conditions
- Asthma, Gastroesophageal Reflux
- Keywords
- Personalized Medicine, CYP2C19, Lansoprazole, Pharmacokinetics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Jason Lang, M.D., M.P.H.University, hospital or other
- Collaborators
- Thrasher Research Fund, Nemours Children's Clinic
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 18 Jan 2024 (actual)
- Study completion
- 18 Jan 2024 (actual)
- First posted
- 10 Jan 2017 (estimated)
- Results
- Posted 9 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: matched placeboparticipants will receive oral blinded matched placebo once daily |
| Genotype-guided Lansoprazole | Experimental | Drug: commercially available lansoprazoleparticipants will receive oral blinded commercially available lansoprazole once daily with a dose appropriate for the participant's metabolizer phenotype |
Who may qualify
- Ages
- 6 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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.
- 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 from the time of enrollment. Participant must be on National Asthma Education and Prevention Program (NAEPP) controller step 2, 3 or 4.
- 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.
Key exclusion criteria (16 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| commercially available lansoprazoleAlso: once dailythese participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily lansoprazole for 24 weeks | Drug | Genotype-guided Lansoprazole |
| matched placeboAlso: once dailythese participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily placebo for 24 weeks | Drug | Placebo |
Primary outcome
Change in Asthma Control Questionnaire (ACQ) From Screening Through Week 26
Time frame: Week 0 (baseline) to week 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. Scores range between 0 (totally controlled) and 6 (severely uncontrolled). Reported is the change from week 0 to week 26; a negative change value indicates an improvement in asthma control.
6 secondary outcomes
Change in GERD (Gastroesophageal Reflux Disease) Symptom Assessment Questionnaire Score (GSAS) From Screening Through Week 26
Time frame: Week 0 (baseline) to week 26
Change in Asthma Symptom Utility Index (ASUI) From Screening Through Week 26
Time frame: Week 0 (baseline) to week 26
Annualized Rate of Asthma Exacerbations
Time frame: Up to week 26
Annualized Rate of Episodes of Poor Asthma Control (EPAC)
Time frame: Up to week 26
Annualized Rate of Respiratory Tract Infection (RTI)
Time frame: Up to week 26
Change in Lung Function Testing From Screening Through Week 26
Time frame: Week -2 (screening) to week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Asthma
RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason E Lang, MD, MPH principal investigator
Duke Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing commercially available lansoprazole in people with Asthma and Gastroesophageal Reflux, run by Jason Lang, M.D., M.P.H. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Asthma Control Questionnaire (ACQ) From Screening Through Week 26 (time frame: Week 0 (baseline) to week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2025.