Lansoprazole to Treat Children With Asthma

NCT00442013 | Completed Phase 4 Results DMC

• 2 other identifiers: 454U01HL080450-01
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 20

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Asthma-specific Quality of Life

  Measured at Weeks 0, 4, 8, 12, 16, 20, 24

• Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

  Measured at Weeks 0, 4, 8, 12, 16, 20, 24

• Rate of Episodes of Poor Asthma Control (EPAC)

  Measured daily for 24 weeks by diary

• Asthma Symptom Utility Index (ASUI)

  Measured at Weeks 0, 4, 8, 12, 16, 20, 24

• Airways Reactivity (Assessed by Methacholine PC20)

  Measured at Weeks 0 and 24

Study Arms (2)

Lansoprazole

EXPERIMENTAL

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

Matching placebo

PLACEBO COMPARATOR

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

Interventions

Lansoprazole DRUG

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.

Also known as: Prevacid

Lansoprazole

Matching placebo DRUG

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.

Also known as: Matching placebo manufactured by TAP Pharmaceuticals

Matching placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• American Lung Association Asthma Clinical Research Centers: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (20)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

National Jewish Medical and Research Center

Denver, Colorado, 80206, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami School of Medicine

Miami, Florida, 33613, United States

Location

University of South Florida College of Medicine

Tampa, Florida, 33613, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Missouri, Kansas City School of Medicine

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

North Shore-Long Island Jewish Health System

New Hyde Park, New York, 11040, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27710, United States

Location

Davis Heart and Lung Research Institute

Columbus, Ohio, 43210, United States

Location

Penn Presbyterain Medical Center/Penn Lung Center

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Vermont Lung Center at The University of Vermont

Burlington, Vermont, 05405, United States

Location

Related Publications (8)

• 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.

  PMID: 22274684 RESULT

• Kaminsky DA, He J, Henderson R, Dixon AE, Irvin CG, Mastronarde J, Smith LJ, Sugar EA, Wise RA, Holbrook JT. Bronchodilator response does not associate with asthma control or symptom burden among patients with poorly controlled asthma. Respir Med. 2023 Nov;218:107375. doi: 10.1016/j.rmed.2023.107375. Epub 2023 Aug 1.

  PMID: 37536444 DERIVED

• 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.

  PMID: 25844821 DERIVED

• 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.

  PMID: 25213052 DERIVED

• 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.

  PMID: 23932458 DERIVED

• 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.

  PMID: 23623526 DERIVED

• 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.

  PMID: 23600541 DERIVED

• 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.

  PMID: 23197288 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Lansoprazole

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Results limited to patients without overt Gastroesophageal reflux disease(GERD). Did not conduct on-treatment potential hydrogen(pH) probe studies to confirm treatment effect. Protein-pump inhibitors(PPI) dose may not induce maximal acid suppression.

Results Point of Contact

• Title: Janet Holbrook
• Organization: Johns Hopkins University

ala-acrc@jhsph.edu

443-287-3170

Study Officials

• Janet Holbrook, PhD, MPH

  Johns Hopkins University School of Public Health

  PRINCIPAL INVESTIGATOR

• Gerald Teague, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 28, 2007
• First Posted: March 1, 2007
• Study Start: March 1, 2007
• Primary Completion: April 1, 2011
• Study Completion: August 1, 2011
• Last Updated: December 6, 2012
• Results First Posted: December 6, 2012

Record last verified: 2012-12

Locations

US (20)