Study of Acid Reflux Therapy for Children With Asthma

Official Title: “Study of Acid Reflux Therapy for Children With Asthma”

Gastroesophageal reflux (GER) is frequent in children with asthma, can induce bronchspasm, and increase airway reactivity. Children with asthma are often treated for GER with drugs to supress gastric acid production. However, this treatment is expensive, and with unproven benefit. The primary objective of this study is to conduct a multi-site, randomized, clinical trial to test the hypothesis that treatment of GER with lansoprazole, an approved proton pump inhibitor, will decrease the frequency of exacerbations in children with poorly controlled asthma. The study will include300 asthmatic children treated with inhaled corticosteroids, 6-16 years of age, with poor control defined by frequent symptoms, excessive beta agonist use, or frequent exacerbations. Participants will be randomly assigned to treatment with either lansoprazole or placebo for 6 months. The presence, severity, and relationship of GER to asthma symptoms will be determined with 24 hour esophageal pH monitoring, but randomization to treatment will not be influenced by the presence or severity of GER. The primary outcome measure is the proportion of participants who have exacerbations of asthma defined by diaries and interviews. Secondary outcome measures include asthma symptom and control scores, GER symptoms, lung function, and unscheduled health care contacts. Pre-defined subgroup analyses will examine the relationship between specific clinical features and the response to lansoprazole. Treatment response will also be evaluated with 3-hour post-dose plasma lansoprazole concentrations, and related to polymorphisms in CYP2C19, the cytochrome P450 pathway, and IL-1 beta, a pro-inflammatory cytokine. Tertiary studies will determine how the magnitude of GER impacts airways inflammation, as measured by the concentrations of H+ (pH) and NO in expired breath.

The results of this trial sould have a major impact on the understanding and treatment of GER in children with asthma.

Intervention(s) in this Clinical Trial

• Drug: lansoprazole
  • participants < 30 kg: 15 mg po once daily
• Drug: placebo
  • participants < 30 kg: 15 mg po once daily participants <= 30 kg: 30 mg po once daily

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: Placebo

Primary Measures

• The proportion of participants who have exacerbations of asthma as defined by diaries and interviews.
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• asthma symptom and control scores
  • Time Frame: 6 months
    Safety Issue?: No
• GER symptoms
  • Time Frame: 6 months
    Safety Issue?: No
• lung function
  • Time Frame: 6 months
    Safety Issue?: No
• unscheduled heathcare contacts
  • Time Frame: within 6 months
    Safety Issue?: No

Inclusion Criteria:Age:

• 6-16 years
• Asthma: Physician diagnosed asthma, mathacholine PC20<16 mg/ml, treatment with a stable dose of daily inhaled corticosteroid equivalent to 200 micrograms/day of fluticasone or greater for 8 weeks or longer
• Poor asthma control: Use of beta-agonist for asthma symptoms twice/week or more, nocturnal awakening with asthma symptoms more than once per week, 2 or more emergency department, unscheduled physician visit, prednisone course, or hospitalizations for asthma in the past 12 months, Score of 1.5 or greater on the Juniper Scale of Recent
• Asthma Control
• Absence of GERD symptoms: No symptoms clearly attributed to GER at the time of enrollment.

Exclusion Criteria:

• Surgery: Previous anti-reflux or peptic ulcer surgery, previous tracheo-esophageal fistula repair
• Pulmonary Function:FEV1 <60% predicted normal as measured immediately before methacholine bronchoprovocation. Methacholine bronchoprovocation limited to participants with an FEV1 >70% of predicted in accordance with FDA indication
• Other major chronic illnesses: 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, renal failure, liver disorders, immunodeficiency states, significant neurodevelopmental delay or behavioral disorders or other conditions that would interfere with participation in the study.
• Medication Use: Anti-reflux medication (proton pump inhibitors, H2 blockers, bethanecol, metaclopromide) within 1 month; Theophylline preparations, azoles, anti-coagulants, insulin, digitalis, any investigative drug within 2 months.
• Drug allergy: Previous adverse effects from lansoprazole, other proton pump inhibitors or methacholine challenge.
• Non-adherence: Inability or unwillingness of the legal guardian to provide consent or inability or unwillingness of the child to provide assent. Inability to swallow study medication. Inability to perform baseline measurements. Less than 80% completion of screening period diaries. Inability to contact by telephone. Intention to move out of the areqa within 6 months. No pregnancy.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 16 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Emory University Other

Overall Clinical Trial Officials and Contacts

William G Teague, MD Principal Investigator Emory University  

Overall Contact: Denise Whitlock 404-717-1733 denise_whitlock@oz.ped.emory.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00604851

Study ID Number: SARCA

ClinicalTrials.gov Identifier: NCT00604851

Health Authority: United States: Institutional Review Board