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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-12-31

Study Completion Date

2008-02-29

Brief Summary

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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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Detailed Description

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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.

Conditions

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Asthma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

salmeterol

Intervention Type DRUG

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

beclomethasone HFA

Intervention Type DRUG

240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

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

Group Type EXPERIMENTAL

salmeterol

Intervention Type DRUG

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

beclomethasone HFA

Intervention Type DRUG

240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

Interventions

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salmeterol

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

Intervention Type DRUG

beclomethasone HFA

240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

Intervention Type DRUG

Other Intervention Names

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Serevent QVAR

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Vernon M. Chinchilli, PhD

Professor and Chair, Department of Public Health Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Homer Boushey

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Mario Castro

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Vernon M. Chinchilli, PhD

Role: PRINCIPAL_INVESTIGATOR

Milton S. Hershey Medical Center

Elliot Israel

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Robert Lemanske

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Richard Martin

Role: PRINCIPAL_INVESTIGATOR

National Jewish Medical & Research Center

Stephen Peters

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Stephen Wasserman

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

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University of California, San Diego

San Diego, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

National Jewish Medical & Research Center

Denver, Colorado, United States

Site Status

Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

University of Wisconsin Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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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. doi: 10.1016/S0140-6736(09)61492-6.

Reference Type RESULT

PMID: 19932356 (View on PubMed)