Genetic Influences of Albuterol Response In Children With Bronchiolitis

Sponsor
Connecticut Children's Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00570297
Collaborator
UConn Health (Other)
55
1
208
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Study Details

Study Description

Brief Summary

Bronchiolitis is a significant cause of morbidity and hospitalization in children, accounting for approximately 125,000 hospitalizations per year in the U.S. Recently, genetic variations of the β2-adrenergic receptor (β2-AR) have been shown to influence response to β2-AR agonist therapy in children with asthma. We suspect that genetic variations of the β2-AR also affect response to β2-AR agonist therapy in children with bronchiolitis.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    Bronchiolitis is a significant cause of morbidity and hospitalization in children, accounting for approximately 125,000 hospitalizations per year in the U.S. Of these hospitalized children, 8% will require intensive care unit (ICU) admission and 67% of these children will require mechanical ventilation. Mortality in previously healthy children is generally low, however, in children with high-risk medical conditions such as prematurity or congenital heart disease, mortality can be as high as 3%. In addition, bronchiolitis infections are associated with long term respiratory problems including development of recurrent wheezing, airway hyperreactivity, and asthma.

    Treatment for bronchiolitis is largely supportive. Despite four decades of clinical trials, there are no therapies demonstrated to be effective in shortening either hospitalization or ICU length of stay in children with bronchiolitis. The use of β2-adrenergic receptor (β2-AR) agonists has received the most attention from investigators, however the results of clinical trials have been contradictory and inconclusive.

    Recently, investigators have shown that genetic factors have important influences on a patient's response to β2-AR agonists. Single nucleotide polymorphisms (SNP) at amino acid position 16 of the β2-AR gene are thought to be the most functionally relevant. A change at base 46 from adenine to guanine results in the amino acid sequence of the β2-AR containing a glycine (Gly), rather than an arginine (Arg), at amino acid position 16. Patients homozygous for Gly at this position (Gly/Gly) have been shown to have improved response to β2-AR agonist therapy when compared to children homozygous for Arginine (Arg/Arg) or heterozygous (Arg/Gly). The next most common polymorphism of the β2-AR gene, glutamine to glutamic acid at position 27 (Glu27Gln), may be associated with the development of asthma and airway hyperresponsiveness, but these relationships are less clear.

    We believe that genetic factors also influence response to β2-AR agonist therapy in children with bronchiolitis. Specifically, we believe that β2-AR polymorphisms at amino acid position 16 affect response to acute β2-AR agonist therapy in children with bronchiolitis. Our hypothesis is that children with bronchiolitis who are homozygous for glycine at amino acid position 16 (Gly/Gly) will have improved response to inhaled β2-AR agonist therapy.

    Study Design

    Study Type:
    Observational
    Anticipated Enrollment :
    55 participants
    Observational Model:
    Case-Only
    Time Perspective:
    Prospective
    Official Title:
    Genetic Influences of Albuterol Response In Children With Bronchiolitis
    Study Start Date :
    Dec 1, 2007
    Anticipated Primary Completion Date :
    Apr 1, 2025
    Anticipated Study Completion Date :
    Apr 1, 2025

    Outcome Measures

    Primary Outcome Measures

    1. Change in lung resistance [Immediate]

      The primary end point is change in lung resistance following a single dose of inhaled b2-AR agonist therapy (albuterol).

    Secondary Outcome Measures

    1. Change in lung compliance [Duration of hospitalization]

      To assess the change in lung compliance following a single dose of inhaled b2-AR agonist therapy (albuterol)

    2. Comparison by genotype [Duration of Hospitalization]

      To compare duration of mechanical ventilation and ICU hospital length of stay by genotype

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 2 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Admission to the CCMC with a primary admission diagnosis of bronchiolitis.

    • Age between 0 and 2 years.

    • Intubated with cuffed endotracheal tube and mechanically ventilated for less than 72 hours.

    • Receiving inhaled albuterol therapy

    Exclusion Criteria:
    • Congenital Heart Defect

    • Immunodeficiency

    • Pre-existing chronic lung disease, including asthma

    • Receiving additional bronchodilator therapy (such as theophylline or ipratropium) or any therapy that would interfere with measuring pulmonary compliance or resistance

    • Receiving Albuterol more frequently than every 4 hours

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Connecticut Children's Medical Center Hartford Connecticut United States 06106

    Sponsors and Collaborators

    • Connecticut Children's Medical Center
    • UConn Health

    Investigators

    • Principal Investigator: Christopher L Carroll, MD, Connecticut Children's Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Christopher Carroll, MD, Associate Professor of Pediatrics, Connecticut Children's Medical Center
    ClinicalTrials.gov Identifier:
    NCT00570297
    Other Study ID Numbers:
    • 07-158
    • UCHC GCRC# 667
    First Posted:
    Dec 10, 2007
    Last Update Posted:
    Jul 12, 2021
    Last Verified:
    Jul 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Christopher Carroll, MD, Associate Professor of Pediatrics, Connecticut Children's Medical Center
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 12, 2021