Lansoprazole to Treat Children With Asthma

Phase 4

Completed

Conditions: Asthma

Interventions: Drug: Matching placebo
Drug: Lansoprazole

Registration Number: NCT00442013

Lead Sponsor: Johns Hopkins University

Brief Summary: Many individuals with asthma also experience gastroesophageal reflux disease (GERD), a condition in which excess stomach acid flows backwards into the esophagus. This study will evaluate the effectiveness of lansoprazole, a medication commonly used to treat GERD in improving asthma control and reducing symptoms in children with poorly controlled asthma.

Detailed Description: Approximately 75% of individuals with asthma also experience GERD. If left untreated, GERD can lead to lung damage, esophageal ulcers, or esophageal cancer. Children and adults whose asthma is poorly controlled with inhaled corticosteroids are often prescribed drugs that suppress gastric acid production; however, this treatment is expensive and has not been proven beneficial. Lansoprazole is a proton pump inhibitor medication that reduces stomach acid production. It may also decrease the frequency of asthma exacerbations in children with poorly controlled asthma. The purpose of this study is to evaluate the effectiveness of lansoprazole at improving asthma control, quality of life, and lung function in children with asthma.

This study will enroll children with poor asthma control who are receiving inhaled corticosteroids. Participants will be randomly assigned to receive either lansoprazole or placebo on a daily basis for 6 months. Study visits will occur at baseline and Weeks 4, 8, 12, 16, 20, and 24, and participants will be contacted by telephone at Week 2. A physical examination, blood collection, and methacholine challenge test will occur at selected visits. The methacholine challenge test will be used to help determine the severity of an individual's asthma. Lung function and airway pressure testing, questionnaires on asthma control and quality of life, medical history review, pill counts, and distribution of medication will occur at most study visits. Participants will record asthma symptoms and lung function in a daily diary throughout the study. A select group of participants will also wear an esophageal potential Hydrogen (pH) monitor for 24 hours to evaluate GERD symptoms and the relationship between GERD and asthma symptoms.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 306

Inclusion Criteria

Physician-diagnosed asthma
At least one of the following lung function criteria must be documented in the year prior to study entry:
1. Bronchial hyperresponsiveness confirmed by 12% or greater improvement in amount of air expired in first second during a forced expiratory maneuver (FEV1) post-bronchodilator, or
2. Methacholine post-diluent baseline (PC20) less than 16 mg/ml, or
3. Exercise bronchoprovocation test with at least a 20% decrease in FEV1
Currently on stable dose of daily inhaled corticosteroid for asthma control (i.e., inhaled corticosteroid equivalent to 2 puffs of 44 ug twice per day [176 ug] of fluticasone or greater for 8 weeks or longer prior to study entry)
Poor asthma control as defined by any one of the following criteria:
1. Use of beta-agonist for asthma symptoms twice a week or more on average in the month prior to study entry
2. Nocturnal awakening with asthma symptoms more than once per week on average in the month prior to study entry
3. Two or more emergency department visits, unscheduled physician visits, prednisone courses, or hospitalizations for asthma in the 12 months prior to study entry
4. Juniper Asthma Control Score (ACS) of 1.25 or greater at the first screening visit
Absence of GERD symptoms at the time of study entry

Exclusion Criteria

Previous anti-reflux or peptic ulcer surgery
Previous tracheoesophageal fistula repair
FEV1 less than 60% of predicted normal value at screening visit and as measured immediately before methacholine bronchoprovocation; methacholine bronchoprovocation will be limited to participants with a FEV1 greater than or equal to 70% of predicted value in accordance with American Thoracic Society (ATS) guidelines
History of a premature birth of less than 33 weeks gestation or any neonate requiring a significant level of respiratory care, including mechanical ventilation
Any major chronic illness, including but not limited to non-skin cancer, cystic fibrosis, bronchiectasis, myelomeningocele, sickle cell anemia, endocrine disease, congenital heart disease, congestive heart failure, stroke, severe hypertension, insulin-dependent diabetes mellitus, kidney failure, liver disorder, immunodeficiency state, significant neuro-developmental delay or behavioral disorder (excluding mild attention deficit hyperactivity disorder), or other condition that would interfere with participation in the study
History of phenylketonuria
Medications for treatment of GI symptoms (e.g., proton pump inhibitors, H2 blockers, bethanechol, metoclopramide) in the month prior to study entry (intermittent anti-acids are allowed)
Use of theophylline preparations, azoles, anti-coagulants, insulin for Type I diabetes, digitalis, or oral iron supplements when administered for iron deficiency in the month prior to study entry
Use of any investigative drug in the 2 months prior to study entry
Previous adverse effects from lansoprazole, other proton pump inhibitors, or sensitivity to aspartame
Inability or unwillingness of the legal guardian to provide consent
Inability or unwillingness of the child to provide assent
Inability to take study medication
Inability to perform baseline measurements
Less than 80% completion of screening period diaries
Inability to contact by telephone
Planning to move out of the area in the 6 months following study entry
Pregnancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Matching placebo	Matching placebo	Participants in this group will receive a matching placebo on a daily basis for 6 months. To maintain masking, there are two doses of the matching placebo provided to participants depending on participant body weight at randomization: 1.) less than 30kg will receive 15mg po once daily or 2.)greater or equal to 30kg 30mg po once daily.
Lansoprazole	Lansoprazole	Participants in this group will receive lansoprazole on a daily basis for 6 months. There are two doses of Lansoprazole solutab provided to participants depending on participant body weight at randomization: 1.) less than 30kg will receive 15mg po once daily or 2.)greater or equal to 30kg 30mg po once daily.

Primary Outcome Measures

Name	Time	Method
Change in Juniper Asthma Control Score (ACS)	Measured at Weeks 0, 4, 8, 12, 24	Score ranges from 0 to 6, a lower score indicated better asthma control. Scores above 1.5 are indicative of poor asthma control; score obtained from questionnaire with 6 questions related to asthma control and FEV (amount of air expired in the first second during a forced expiratory maneuver); number presents an average of the change from baseline to all follow-up points

Secondary Outcome Measures

Name	Time	Method
Asthma-specific Quality of Life	Measured at Weeks 0, 4, 8, 12, 16, 20, 24	Scores range from 1 to 7 with higher values indicating better asthma-related quality of life; questionnaire measures functional impairments that are most troublesome to children as a result of their asthma; number presents an average of the change from baseline to all follow-up points
Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Measured at Weeks 0, 4, 8, 12, 16, 20, 24	A measure of pulmonary function, specifically the amount of expired air in the first second during a forced expiratory maneuver while seated; test performed at least 4 hours after last dose of short-acting bronchodilator and at least 12 hours after long-acting bronchodilator; number presents an average of the change from baseline to all follow-up points
Rate of Episodes of Poor Asthma Control (EPAC)	Measured daily for 24 weeks by diary	Episodes of poor asthma control are defined as any one of the following: * 2 consecutive days with peak flow at less than 70% of baseline * prescription of oral corticosteroids for asthma * seeking urgent medical care for asthma symptoms EPAC was measured by review of daily diaries that were maintained over the entire course of followup, i.e, 24 weeks
Asthma Symptom Utility Index (ASUI)	Measured at Weeks 0, 4, 8, 12, 16, 20, 24	ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control; info obtained from questionnaire about asthma symptoms; number presents an average of the change from baseline to all follow-up points
Airways Reactivity (Assessed by Methacholine PC20)	Measured at Weeks 0 and 24	Presence and degree of airway hyperresponsiveness; change from baseline to 24 weeks for airways reactivity assessed by methacholine post-diluent baseline (PC20) after medication holds

Trial Locations

Locations (20): University of Miami School of Medicine
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Miami, Florida, United States
Indiana University
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Indianapolis, Indiana, United States
Washington University School of Medicine
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St. Louis, Missouri, United States
Duke University School of Medicine
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Durham, North Carolina, United States
New York University School of Medicine
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New York, New York, United States
University of Minnesota
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Minneapolis, Minnesota, United States
Nemours Children's Clinic
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Jacksonville, Florida, United States
National Jewish Medical and Research Center
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Denver, Colorado, United States
University of South Florida College of Medicine
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Tampa, Florida, United States
University of Alabama at Birmingham
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Birmingham, Alabama, United States
University of California San Diego
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San Diego, California, United States
Emory University School of Medicine
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Atlanta, Georgia, United States
Northwestern Memorial Hospital
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Chicago, Illinois, United States
Penn Presbyterain Medical Center/Penn Lung Center
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Philadelphia, Pennsylvania, United States
North Shore-Long Island Jewish Health System
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New Hyde Park, New York, United States
New York Medical College
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Valhalla, New York, United States
Davis Heart and Lung Research Institute
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Columbus, Ohio, United States
Vermont Lung Center at The University of Vermont
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Burlington, Vermont, United States
University of Missouri, Kansas City School of Medicine
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Kansas City, Missouri, United States
Baylor College of Medicine
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Houston, Texas, United States