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Completed

NCT Number: NCT00200967

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.

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Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of California, San Diego, San Diego, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Salmeterol

Drug

50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)

Other names: Serevent

beclomethasone HFA

Drug

240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

Other names: QVAR

Primary outcomes

  1. 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

    Change between placebo salmeterol and active salmeterol for AM PEF rate

Secondary outcomes

  1. 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

    Change between placebo salmeterol and active salmeterol for PM PEF rate

  2. 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

    Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)

  3. 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

    Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).

  4. 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

    Change between placebo salmeterol and active salmeterol for rescue medication use

  5. 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

    Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator

  6. Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator

    Time frame: 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

  7. 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

    Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator

  8. Exhaled Nitric Oxide (eNO)

    Time frame: Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

    Change between placebo salmeterol and active salmeterol for eNO

  9. Exhaled Breath Condensate (EBC)

    Time frame: Clinic visits at weeks 0, 10, and 18 of each treatment period

    Change between placebo salmeterol and active salmeterol for EBC

  10. Methacholine Provocative Concentration 20 (PC20)

    Time frame: Clinic visits at weeks 0 and 18 of each treatment period

    Change between placebo salmeterol and active salmeterol for methacholine PC20

  11. Asthma Control Questionnaire (ACQ)

    Time frame: 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).

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Collaborators

  • Asthma Clinical Research Network
  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Important dates

Study start
2004
Primary completion
2008
Study completion
2008
First posted
Sep 20, 2005
Registry last updated
Jan 23, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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