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Genetic Influences of Albuterol Response In Children With Bronchiolitis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Connecticut Health Center
Information provided by (Responsible Party):
Christopher Carroll, MD, Connecticut Children's Medical Center
ClinicalTrials.gov Identifier:
NCT00570297
First received: December 6, 2007
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

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
Bronchiolitis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Genetic Influences of Albuterol Response In Children With Bronchiolitis

Resource links provided by NLM:


Further study details as provided by Connecticut Children's Medical Center:

Primary Outcome Measures:
  • The primary end point is change in lung resistance following a single dose of inhaled b2-AR agonist therapy (albuterol). [ Time Frame: Immediate ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the change in lung compliance following a single dose of inhaled b2-AR agonist therapy (albuterol) [ Time Frame: Duration of hospitalization ] [ Designated as safety issue: No ]
  • To compare duration of mechanical ventilation and ICU hospital length of stay by genotype [ Time Frame: Duration of Hospitalization ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: December 2007
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 2 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Children hospitalized in the intensive care unit with bronchiolitis

Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570297

Locations
United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
Sponsors and Collaborators
Connecticut Children's Medical Center
University of Connecticut Health Center
Investigators
Principal Investigator: Christopher L Carroll, MD Connecticut Children's Medical Center
  More Information

No publications provided

Responsible Party: Christopher Carroll, MD, Associate Professor of Pediatrics, Connecticut Children's Medical Center
ClinicalTrials.gov Identifier: NCT00570297     History of Changes
Other Study ID Numbers: 07-158, UCHC GCRC# 667
Study First Received: December 6, 2007
Last Updated: February 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Connecticut Children's Medical Center:
Pediatric
Polymorphism, Genetic
Adrenergic beta-Agonists

Additional relevant MeSH terms:
Bronchiolitis
Bronchial Diseases
Bronchitis
Lung Diseases
Lung Diseases, Obstructive
Respiratory Tract Diseases
Respiratory Tract Infections

ClinicalTrials.gov processed this record on November 23, 2014