Clinical trial NCT00442013: Lansoprazole to Treat Children With Asthma
Official title: Phase III: The Study of Acid Reflux in Children With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: American Lung Association Asthma Clinical Research Centers
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-03-01
Enrollment: 306
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Juniper Asthma Control Score (ACS)
timeFrame: Measured at Weeks 0, 4, 8, 12, 24
Secondary outcomes:
measure: Asthma-specific Quality of Life
timeFrame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
measure: Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
measure: Rate of Episodes of Poor Asthma Control (EPAC)
timeFrame: Measured daily for 24 weeks by diary
measure: Asthma Symptom Utility Index (ASUI)
timeFrame: Measured at Weeks 0, 4, 8, 12, 16, 20, 24
measure: Airways Reactivity (Assessed by Methacholine PC20)
timeFrame: Measured at Weeks 0 and 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Denver
country: United States
facility: National Jewish Medical and Research Center
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida College of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: University of Missouri, Kansas City School of Medicine
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Hyde Park
country: United States
facility: North Shore-Long Island Jewish Health System
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Columbus
country: United States
facility: Davis Heart and Lung Research Institute
state: Ohio
city: Philadelphia
country: United States
facility: Penn Presbyterain Medical Center/Penn Lung Center
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Burlington
country: United States
facility: Vermont Lung Center at The University of Vermont
state: Vermont
Study officials:
affiliation: Johns Hopkins University School of Public Health
name: Janet Holbrook, PhD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Gerald Teague, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Writing Committee for the American Lung Association Asthma Clinical Research Centers; Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, Castro M, Dozor AJ, Lima JJ, Mastronarde JG, Sockrider MM, Teague WG. Lansoprazole for children with poorly controlled asthma: a randomized controlled trial. JAMA. 2012 Jan 25;307(4):373-81. doi: 10.1001/jama.2011.2035.
citation: Fitzpatrick AM, Holbrook JT, Wei CY, Brown MS, Wise RA, Teague WG; American Lung Association's Asthma Clinical Research Centers Network. Exhaled breath condensate pH does not discriminate asymptomatic gastroesophageal reflux or the response to lansoprazole treatment in children with poorly controlled asthma. J Allergy Clin Immunol Pract. 2014 Sep-Oct;2(5):579-86.e7. doi: 10.1016/j.jaip.2014.04.006. Epub 2014 May 21.
citation: Nguyen JM, Holbrook JT, Wei CY, Gerald LB, Teague WG, Wise RA; American Lung Association Asthma Clinical Research Centers. Validation and psychometric properties of the Asthma Control Questionnaire among children. J Allergy Clin Immunol. 2014 Jan;133(1):91-7.e1-6. doi: 10.1016/j.jaci.2013.06.029. Epub 2013 Aug 6.
citation: Blake K, Teague WG. Gastroesophageal reflux disease and childhood asthma. Curr Opin Pulm Med. 2013 Jan;19(1):24-9. doi: 10.1097/MCP.0b013e32835b582b.
citation: Lang JE, Holbrook JT, Mougey EB, Wei CY, Wise RA, Teague WG, Lima JJ; American Lung Association-Airways Clinical Research Centers. Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype. Ann Am Thorac Soc. 2015 Jun;12(6):878-85. doi: 10.1513/AnnalsATS.201408-391OC.
citation: Lima JJ, Lang JE, Mougey EB, Blake KB, Gong Y, Holbrook JT, Wise RA, Teague WG. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr. 2013 Sep;163(3):686-91. doi: 10.1016/j.jpeds.2013.03.017. Epub 2013 Apr 24.
citation: Mougey E, Lang JE, Allayee H, Teague WG, Dozor AJ, Wise RA, Lima JJ. ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma. Clin Exp Allergy. 2013 May;43(5):512-20. doi: 10.1111/cea.12076.