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

NCT ID: NCT03015610

Last Updated: 2025-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-31
• Study Completion Date: 2024-01-18

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

participants will receive oral blinded matched placebo once daily

Group Type: PLACEBO_COMPARATOR

matched placebo

Intervention Type: DRUG

these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily placebo for 24 weeks

Genotype-guided Lansoprazole

participants will receive oral blinded commercially available lansoprazole once daily with a dose appropriate for the participant's metabolizer phenotype

Group Type: EXPERIMENTAL

commercially available lansoprazole

Intervention Type: DRUG

these participants will receive a one-time dose of lansoprazole followed by PK analysis and then once daily lansoprazole for 24 weeks

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

once daily; once daily

Eligibility Criteria

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 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.

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

Nemours Children's Clinic

OTHER

Sponsor Role: collaborator

Jason Lang, M.D., M.P.H.

OTHER

Sponsor Role: lead

Responsible Party

Jason Lang, M.D., M.P.H.

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jason E Lang, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

Nemours Children's Specialty Care

Jacksonville, Florida, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00079073

Identifier Type: -

Identifier Source: org_study_id