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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: October 2010

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 pH monitor for 24 hours to evaluate GERD symptoms and the relationship between GERD and asthma symptoms.

Intervention(s) in this Clinical Trial

• Drug: Lansoprazole
  • 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.
• Other: Placebo
  • Participants will receive a placebo pill on a daily basis.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive lansoprazole on a daily basis for 6 months.
• Placebo Comparator: 2
  • Participants will receive placebo on a daily basis for 6 months.

Primary Measures

• Change in Juniper Asthma Control Score (ACS)
  • Time Frame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
    Safety Issue?: No

Secondary Measures

• Asthma-specific quality of life
  • Time Frame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
    Safety Issue?: No
• Lung function measures (assessed by spirometry)
  • Time Frame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
    Safety Issue?: No
• Rate of episodes of poor asthma control (EPAC)
  • Time Frame: Measured daily by diary
    Safety Issue?: No
• Asthma symptom utility index
  • Time Frame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
    Safety Issue?: No
• Airways reactivity (assessed by methacholine PC20)
  • Time Frame: Measured at Weeks 0 and 24
    Safety Issue?: No

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 FEV1 post-bronchodilator, or 2. Methacholine 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 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 tracheo-esophageal 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

Janet Holbrook, PhD, MPH Principal Investigator Johns Hopkins University School of Public Health  

Overall Contact: Ellen Brown, MS 410-955-3118 ala-acrc@jhsph.edu

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00442013

Study ID Number: 454

ClinicalTrials.gov Identifier: NCT00442013

Health Authority: United States: Federal Government