Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)

Asthma Clinical Trial

Official title:

Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00200967
• Other study ID #: 262
• Secondary ID: 5U10HL074231U10H
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: December 26, 2017
• Start date: December 2004
• Est. completion date: February 2008

Study information

• Verified date: December 2017
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• salmeterol
50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)
• beclomethasone HFA
240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	National Jewish Medical & Research Center	Denver	Colorado
United States	University of Wisconsin Madison	Madison	Wisconsin
United States	Washington University	Saint Louis	Missouri
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	Asthma Clinical Research Network, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, Ameredes BT, Castro M, Craig TJ, Denlinger L, Fahy JV, Jarjour N, Kazani S, Kim S, Kraft M, Lazarus SC, Lemanske RF Jr, Markezich A, Martin RJ, Permaul P, Peters SP, Ramsdell J, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morning (AM) Peak Expiratory Flow (PEF) Rate	Change between placebo salmeterol and active salmeterol for AM 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
Secondary	Evening (PM) Peak Expiratory Flow (PEF) Rate	Change between placebo salmeterol and active salmeterol for PM 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
Secondary	Peak Expiratory Flow (PEF) Variability	Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)	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
Secondary	Asthma Symptoms	Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).	Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Rescue Medication (Ipratropium and Albuterol) Use	Change between placebo salmeterol and active salmeterol for rescue medication use	Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator	Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator	Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator	Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator	Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator	Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator	Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Exhaled Nitric Oxide (eNO)	Change between placebo salmeterol and active salmeterol for eNO	Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Secondary	Exhaled Breath Condensate (EBC)	Change between placebo salmeterol and active salmeterol for EBC	Clinic visits at weeks 0, 10, and 18 of each treatment period
Secondary	Methacholine Provocative Concentration 20 (PC20)	Change between placebo salmeterol and active salmeterol for methacholine PC20	Clinic visits at weeks 0 and 18 of each treatment period
Secondary	Asthma Control Questionnaire (ACQ)	Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).	Clinic visits at weeks 0 and 18 of each treatment period

External Links

•   Asthma Clinical Research Network (ACRN) Website