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
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: salmeterol
Drug: beclomethasone HFA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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).


Enrollment: 87
Study Start Date: December 2004
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 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
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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00200967

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143-0130
United States, Colorado
National Jewish Medical & Research Center
Denver, Colorado, United States, 80206
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, North Carolina
Wake Forest University Health Sciences
Winston Salem, North Carolina, United States, 27103
United States, Wisconsin
University of Wisconsin Madison
Madison, Wisconsin, United States, 53792-3244
Sponsors and Collaborators
Milton S. Hershey Medical Center
Asthma Clinical Research Network
Investigators
Principal Investigator: Homer Boushey University of California, San Francisco
Principal Investigator: Mario Castro Washington University Early Recognition Center
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
  More Information

Additional Information:
Publications:
Responsible Party: Vernon M. Chinchilli, PhD, Professor and Chair, Department of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00200967     History of Changes
Other Study ID Numbers: 262, 5U10HL074231, U10 HL074073, U10 HL074204, U10 HL074208, U10 HL074212, U10 HL074218, U10 HL074225, U10 HL074227, U10 HL074231
Study First Received: September 12, 2005
Results First Received: March 5, 2009
Last Updated: February 24, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Beclomethasone
Salmeterol
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014