Lansoprazole to Treat Children With Asthma (SARCA)

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 Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Lansoprazole; Drug: Matching placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • San Diego, California, United States, 92103
      • University of California San Diego
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33613
      • University of Miami School of Medicine
    • Tampa, Florida, United States, 33613
      • University of South Florida College of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • University of Missouri, Kansas City School of Medicine
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore-Long Island Jewish Health System
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Davis Heart and Lung Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterain Medical Center/Penn Lung Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Vermont Lung Center at The University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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 Names: Prevacid
Placebo Comparator: 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.	Drug: Matching placebo; 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.; Other Names: Matching placebo manufactured by TAP Pharmaceuticals

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Lung Association Asthma Clinical Research Centers
• Investigators: Principal Investigator: Janet Holbrook, PhD, MPH, Johns Hopkins University School of Public Health; Principal Investigator: Gerald Teague, MD, University of Virginia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: February 28, 2007
• First Submitted That Met QC Criteria: February 28, 2007
• First Posted (Estimate): March 1, 2007

Study Record Updates

• Last Update Posted (Estimate): December 6, 2012
• Last Update Submitted That Met QC Criteria: December 5, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Dexlansoprazole; Lansoprazole
• Other Study ID Numbers: 454; U01HL080450-01 (U.S. NIH Grant/Contract)