Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
This study has been completed.
Sponsor:
Milton S. Hershey Medical Center
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
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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:
MedlinePlus related topics:
Asthma
Drug Information available for:
Beclomethasone dipropionate
Beclomethasone dipropionate monohydrate
Salmeterol
Salmeterol xinafoate
U.S. FDA Resources
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
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 School of Medicine |
| 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 University |
| 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 Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents |
ClinicalTrials.gov processed this record on June 18, 2013