Lansoprazole to Treat Children With Asthma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase III: The Study of Acid Reflux in Children With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed asthma At least one of the following lung function criteria must be documented in the year prior to study entry: 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 Methacholine post-diluent baseline (PC20) less than 16 mg/ml, or 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: Use of beta-agonist for asthma symptoms twice a week or more on average in the month prior to study entry Nocturnal awakening with asthma symptoms more than once per week on average in the month prior to study entry Two or more emergency department visits, unscheduled physician visits, prednisone courses, or hospitalizations for asthma in the 12 months prior to study entry 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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lansoprazole<br>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. | Drug: Lansoprazole<br>* Participants less than 30 kg will receive 15 mg a day, by mouth; participants greater than or equal to 30 kg will receive 30 mg a day, by mouth.<br>* Other names: Prevacid;|
| Placebo Comparator: Matching placebo<br>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. | Drug: Matching placebo<br>* Participants will receive a placebo pill on a daily basis. 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.<br>* Other names: Matching placebo manufactured by TAP Pharmaceuticals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Juniper Asthma Control Score (ACS) | 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 | Measured at Weeks 0, 4, 8, 12, 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma-specific Quality of Life | 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 | Measured at Weeks 0, 4, 8, 12, 16, 20, 24 | 
| Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | 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 | Measured at Weeks 0, 4, 8, 12, 16, 20, 24 | 
| Rate of Episodes of Poor Asthma Control (EPAC) | 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 | Measured daily for 24 weeks by diary | 
| Asthma Symptom Utility Index (ASUI) | 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 | Measured at Weeks 0, 4, 8, 12, 16, 20, 24 | 
| Airways Reactivity (Assessed by Methacholine PC20) | 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 | Measured at Weeks 0 and 24 |