Asthma Clinical Research Network (ACRN) Beta Adrenergic Response by Genotype (BARGE)
Clinical Trials URL:
Study Type: Clinical Trial
Prepared on May 20, 2009
Last Updated on August 24, 2006
Study Dates: 1993-2008
Consent: Unrestricted Consent
Commercial Use Restrictions: No
Collection Type: Open BioLINCC Study - See bottom of this webpage for request information
This project examined the use of regularly scheduled albuterol treatment in asthma, in a genotype-stratified, randomised, placebo-controlled cross-over trial in patients with mild asthma.
The issue of whether regular use of an inhaled beta-adrenergic agonist worsens airflow and clinical outcomes in asthma is controversial. Retrospective studies have suggested that adverse effects occur in patients with a genetic polymorphism that results in homozygosity for arginine (Arg/Arg), rather than glycine (Gly/Gly), at aminoacid residue 16 of the beta-adrenergic receptor. However, the existence of any genotype-dependent difference has not been tested in a prospective clinical trial.
A total of 338 Patients with mild asthma, 18-55 years of age, reporting use of inhaled beta agonist of less than 56 puffs per week as their only asthma treatment and with a forced expiratory volume in one second that was at least 70% of predicted were screened. Screened patients were then genotyped and those patients homozygous for Arg/Arg or Gly/Gly at the 16th aminoacid residue of the beta 2 adrenergic receptor were eligible for the study (180 patients). Of those eligible, 94 patients were matched and enrolled at the first visit (42 Arg/Arg and 52 Gly/Gly) and 78 were randomized (Arg/Arg n=37, four of 41 matches withdrew before randomisation; Gly/Gly n=41). Regularly scheduled treatment with albuterol or placebo was given in a masked, cross-over design, for 16-week periods.
Genotype at the 16th aminoacid residue of the beta-adrenergic receptor affects the long-term response to albuterol use. Bronchodilator treatments avoiding albuterol may be appropriate for patients with the Arg/Arg genotype (Lancet 2004; 364: 1505-12).