Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 7
- 主要终点
- Morning (AM) Peak Expiratory Flow (PEF) Rate
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
B16 Arg/Arg
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
干预措施: salmeterol (Drug)
B16 Arg/Arg
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
干预措施: beclomethasone HFA (Drug)
B16 Gly/Gly
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
干预措施: salmeterol (Drug)
B16 Gly/Gly
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
干预措施: beclomethasone HFA (Drug)
结局指标
主要结局
Morning (AM) Peak Expiratory Flow (PEF) Rate
时间窗: 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
次要结局
- 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)
- Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator(Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period)
- Asthma Control Questionnaire (ACQ)(Clinic visits at weeks 0 and 18 of each treatment period)
- Asthma Symptoms(Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period)
- 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)
- Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator(Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period)
- 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)
- 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)
- Exhaled Nitric Oxide (eNO)(Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period)
- Exhaled Breath Condensate (EBC)(Clinic visits at weeks 0, 10, and 18 of each treatment period)
- Methacholine Provocative Concentration 20 (PC20)(Clinic visits at weeks 0 and 18 of each treatment period)
研究者
Vernon M. Chinchilli, PhD
Professor and Chair, Department of Public Health Sciences
Milton S. Hershey Medical Center