Asthma Clinical Research Network Trial (ACRN) - Long-Acting Beta Agonist Response by Genotype (LARGE)
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December 2004 – February 2008
Dataset(s) Last Updated
January 3, 2018
Clinical Trial URLs
Primary Publication URLs
Commercial Use Data Restrictions No
Data Restrictions Based On Area Of Research No
The purpose of this trial was to determine whether regularly scheduled use of an inhaled long-acting beta agonist (salmeterol) in the setting of concomitant use of inhaled corticosteroids (beclomethasone hydroflouroalkane (HFA) inhaler) would have a detrimental effect on asthma control in people who bear the B16 Arg/Arg genotype of the beta-2 adrenergic receptor gene, as compared to people with asthma of similar severity who bear the B16 Gly/Gly genotype.
Some studies suggest that patients with asthma who are homozygous for arginine at the 16th amino acid position of the beta-2 adrenergic receptor (B16 Arg/Arg) benefit less from treatment with long acting beta-2 agonists and inhaled corticosteroids than do those homozygous for glycine (B16 Gly/Gly). This study investigated whether there is a genotype-specific response to treatment with a long acting beta-2 agonist in combination with inhaled corticosteroid.
Subjects were adult patients with moderate asthma who were homozygous for arginine or glycine at the 16th amino acid position of the beta-2 adrenergic receptor (B16 Arg/Arg or B16 Gly/Gly). Individuals were matched against their opposite genotype by forced expiratory volume in one second (FEV1) and race. A total of 474 patients were screened for the trial between 2004 and 2006. Eighty-seven were randomized (42 with the B16 Arg/Arg genotype and 45 with the B16 Gly/Gly genotype).
In this multicenter, randomized, double-blind, placebo-controlled trial individuals in a matched pair were randomly assigned by computer-generated randomization sequence to receive inhaled long acting beta-2 agonist (salmeterol 50 micrograms twice a day) or placebo given in a double-blind, crossover design for two 18-week periods. Open-label inhaled corticosteroid (hydrofluoroalkane beclometasone 240 micrograms twice a day) was given to all participants during the treatment periods. The primary endpoint was morning peak expiratory flow (PEF). Analysis was by intention to treat.
In asthma patients with B16 Arg/Arg and B16 Gly/Gly genotypes, combination treatment with salmeterol and inhaled corticosteroid improved airway function when compared with inhaled corticosteroid therapy alone. These findings suggest that patients should continue to be treated with long acting beta-2 agonists plus moderate-dose inhaled corticosteroids irrespective of B16 genotype. Further investigation is needed to establish the importance of the genotype-specific difference in responsiveness to methacholine (Lancet, 2009; 374(9703): 1754-64).
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