Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
The purpose of this trial is 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) will 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.
BACKGROUND:

 The purpose of this study is to compare the effects of a long-acting beta agonist in patients
 with asthma receiving inhaled corticosteroids who express two distinct polymorphisms of the
 beta-2 adrenergic receptor.

 DESIGN NARRATIVE:

 Participants were homozygous for arginine or glycine at the 16th amino-acid position of the
 β-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. Matched
 participants entered an 8-week run-in period. This is a 62-week crossover design where
 subjects receive the following therapies:

 -  Beclomethasone HFA (240 µg twice a day (BID)) + as-needed (PRN) albuterol: 8-week run-in

 -  Beclomethasone HFA (240 µg BID) + salmeterol (50 µg BID) + PRN ipratropium bromide + PRN
 albuterol: 18-week treatment period

 -  Beclomethasone HFA (240 µg BID) + PRN albuterol: 8-week run-out

 -  Beclomethasone HFA (240 µg BID) + placebo salmeterol + PRN ipratropium bromide + PRN
 albuterol: 18-week treatment period

 -  Beclomethasone HFA (240 µg BID) + PRN albuterol: 10-week run-out

 The order of treatments received during the two treatment periods is randomized.
Inclusion Criteria:

 -  Male or female, ages 18 and older

 -  Clinical history consistent with asthma

 -  For subjects regularly using inhaled corticosteroids, FEV1 50% of predicted,
 methacholine PC20 FEV1 16 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs
 of inhaled albuterol

 -  For subjects not regularly using inhaled corticosteroids, FEV1 40% of predicted,
 methacholine PC20 FEV1 8 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs of
 inhaled albuterol

 -  Genotype eligibility (determined during screening)

 Exclusion Criteria:

 -  Smoker (total smoking history must be less than 10 pack years)

 -  Significant unstable medical condition other than asthma

 -  History of life-threatening asthma requiring treatment with intubation and mechanical
 ventilation in the past 10 years

 -  Pregnant or lactating