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

This study has been completed.
Sponsor:
Collaborators:
Asthma Clinical Research Network
Information provided by (Responsible Party):
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00200967
First received: September 12, 2005
Last updated: February 24, 2013
Last verified: February 2013

September 12, 2005
February 24, 2013
December 2004
February 2008   (final data collection date for primary outcome measure)
Morning (AM) Peak Expiratory Flow (PEF) Rate [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
Change between placebo salmeterol and active salmeterol for AM PEF rate
Not Provided
Complete list of historical versions of study NCT00200967 on ClinicalTrials.gov Archive Site
  • Evening (PM) Peak Expiratory Flow (PEF) Rate [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Change between placebo salmeterol and active salmeterol for PM PEF rate
  • Peak Expiratory Flow (PEF) Variability [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)
  • Asthma Symptoms [ Time Frame: Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: Yes ]
    Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).
  • Rescue Medication (Ipratropium and Albuterol) Use [ Time Frame: Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: Yes ]
    Change between placebo salmeterol and active salmeterol for rescue medication use
  • Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator
  • Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator
  • Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator
  • Exhaled Nitric Oxide (eNO) [ Time Frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for eNO
  • Exhaled Breath Condensate (EBC) [ Time Frame: Clinic visits at weeks 0, 10, and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for EBC
  • Methacholine Provocative Concentration 20 (PC20) [ Time Frame: Clinic visits at weeks 0 and 18 of each treatment period ] [ Designated as safety issue: No ]
    Change between placebo salmeterol and active salmeterol for methacholine PC20
  • Asthma Control Questionnaire (ACQ) [ Time Frame: Clinic visits at weeks 0 and 18 of each treatment period ] [ Designated as safety issue: Yes ]
    Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).
Not Provided
Not Provided
Not Provided
 
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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Asthma
  • Drug: salmeterol
    50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)
    Other Name: Serevent
  • Drug: beclomethasone HFA
    240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)
    Other Name: QVAR
  • Experimental: 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
    Interventions:
    • Drug: salmeterol
    • Drug: beclomethasone HFA
  • Experimental: 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
    Interventions:
    • Drug: salmeterol
    • Drug: beclomethasone HFA
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, Sorkness CA, Sutherland ER, Szefler SJ, Walter MJ, Wasserman SI, Israel E; National Heart, Lung and Blood Institute's Asthma Clinical Research Network. Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009 Nov 21;374(9703):1754-64.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
87
February 2008
February 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00200967
262, 5U10HL074231, U10 HL074073, U10 HL074204, U10 HL074208, U10 HL074212, U10 HL074218, U10 HL074225, U10 HL074227, U10 HL074231
Yes
Vernon M. Chinchilli, PhD, Milton S. Hershey Medical Center
Milton S. Hershey Medical Center
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Asthma Clinical Research Network
Principal Investigator: Homer Boushey University of California, San Francisco
Principal Investigator: Mario Castro Washington University
Principal Investigator: Vernon M. Chinchilli, PhD Milton S. Hershey Medical Center
Principal Investigator: Elliot Israel Brigham and Women's Hospital
Principal Investigator: Robert Lemanske University of Wisconsin, Madison
Principal Investigator: Richard Martin National Jewish Medical & Research Center
Principal Investigator: Stephen Peters Wake Forest School of Medicine
Principal Investigator: Stephen Wasserman University of California, San Diego
Milton S. Hershey Medical Center
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP