Lansoprazole to Treat Children With Asthma

NCT ID: NCT00442013

Last Updated: 2012-12-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

306 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2011-08-31

Brief Summary

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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

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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.

Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Lansoprazole

Intervention Type 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.

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.

Group Type PLACEBO_COMPARATOR

Matching placebo

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Prevacid Matching placebo manufactured by TAP Pharmaceuticals

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American Lung Association Asthma Clinical Research Centers

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Janet Holbrook

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Janet Holbrook, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University School of Public Health

Gerald Teague, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

National Jewish Medical and Research Center

Denver, Colorado, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami School of Medicine

Miami, Florida, United States

Site Status

University of South Florida College of Medicine

Tampa, Florida, United States

Site Status

Emory University School of Medicine

Atlanta, Georgia, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Missouri, Kansas City School of Medicine

Kansas City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

North Shore-Long Island Jewish Health System

New Hyde Park, New York, United States

Site Status

New York University School of Medicine

New York, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Duke University School of Medicine

Durham, North Carolina, United States

Site Status

Davis Heart and Lung Research Institute

Columbus, Ohio, United States

Site Status

Penn Presbyterain Medical Center/Penn Lung Center

Philadelphia, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Vermont Lung Center at The University of Vermont

Burlington, Vermont, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 22274684 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37536444 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25844821 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25213052 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23932458 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23623526 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23600541 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23197288 (View on PubMed)

Other Identifiers

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U01HL080450-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

454

Identifier Type: -

Identifier Source: org_study_id

NCT00604851

Identifier Type: -

Identifier Source: nct_alias