- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00570297
Genetic Influences of Albuterol Response In Children With Bronchiolitis
Study Overview
Status
Conditions
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 Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Connecticut
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Hartford, Connecticut, United States, 06106
- Connecticut Children's Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change in lung resistance
Time Frame: Immediate
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The primary end point is change in lung resistance following a single dose of inhaled b2-AR agonist therapy (albuterol).
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Immediate
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in lung compliance
Time Frame: Duration of hospitalization
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To assess the change in lung compliance following a single dose of inhaled b2-AR agonist therapy (albuterol)
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Duration of hospitalization
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Comparison by genotype
Time Frame: Duration of Hospitalization
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To compare duration of mechanical ventilation and ICU hospital length of stay by genotype
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Duration of Hospitalization
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Christopher L Carroll, MD, Connecticut Children's Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 07-158
- UCHC GCRC# 667 (Other Identifier: University of Connecticut Health Center)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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