Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
- Registration Number
- NCT00200967
- Lead Sponsor
- Milton S. Hershey Medical Center
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 87
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description B16 Gly/Gly beclomethasone HFA B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA B16 Arg/Arg beclomethasone HFA B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA B16 Arg/Arg salmeterol B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA B16 Gly/Gly salmeterol B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
- Primary Outcome Measures
Name Time Method Morning (AM) Peak Expiratory Flow (PEF) Rate Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for AM PEF rate
- Secondary Outcome Measures
Name Time Method Evening (PM) Peak Expiratory Flow (PEF) Rate Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for PM PEF rate
Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator
Asthma Control Questionnaire (ACQ) Clinic visits at weeks 0 and 18 of each treatment period Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).
Asthma Symptoms Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).
Rescue Medication (Ipratropium and Albuterol) Use Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for rescue medication use
Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator
Peak Expiratory Flow (PEF) Variability Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)
Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator
Exhaled Nitric Oxide (eNO) Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for eNO
Exhaled Breath Condensate (EBC) Clinic visits at weeks 0, 10, and 18 of each treatment period Change between placebo salmeterol and active salmeterol for EBC
Methacholine Provocative Concentration 20 (PC20) Clinic visits at weeks 0 and 18 of each treatment period Change between placebo salmeterol and active salmeterol for methacholine PC20
Trial Locations
- Locations (7)
University of California, San Diego
🇺🇸San Diego, California, United States
Brigham & Women's Hospital
🇺🇸Boston, Massachusetts, United States
National Jewish Medical & Research Center
🇺🇸Denver, Colorado, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Wisconsin Madison
🇺🇸Madison, Wisconsin, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States