Clinical trial NCT00521222: Evaluating Long Acting Beta Agonists Used to Treat Asthma Among Those With Either Arg/Arg or Gly/Gly Genotypes
Official title: Arg/Arg Genotype and Long Acting Beta Agonists in Asthma. Improved Quality of Care for Patients With Asthma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: asthma
beta agonist
bronchodilator
pulmonary
genotype
pharmacogenomics
corticosteroid
allergy
immunology
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2007-08-27
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators are conducting a study of asthma patients who use fluticasone with salmeterol (Advair) or any other combination of an inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) to manage their asthma symptoms.

Participants begin the study by continuing to use fluticasone with salmeterol or substituting fluticasone with salmeterol for their current ICS/LABA medication at their regular dose or the comparable dose(all study medications are provided) for a six-week period. Patients are then separated into 2 groups: one group is asked to use fluticasone (Flovent), the other to use fluticasone with salmeterol , twice daily over a 16-week period (patients will need to be seen monthly during this time). Neither study personnel nor patients will know which drug is being used.

Patients are also asked to use a peak flow meter and record their daily results on a form, along with the number of puffs they use of their rescue inhaler each day. They also record any changes in asthma medications and information on any asthma episodes.

The investigators hypothesize that there are certain patients with asthma who will do better when a long acting beta agonist is removed from their maintenance asthma medications.

Detailed description: Beta 2 (b2) agonists are the most common type of bronchodilator used to treat asthma. Beta 2 (b2) agonists are agents that bind to b2 receptors and cause muscle relaxation of the airways. There are different variants of the gene (genotypes) that influence how b2 agonists perform among the population.

A recent study demonstrated that patients with mild asthma and the Arg/Arg variant at the 16th amino acid position have improved lung function and asthma control when albuterol (Proventil-HFA), a short acting b2 agonist, is replaced with a different class of bronchodilator. The investigators plan to study asthma patients with distinct genetic makeups of the b2 receptor; specifically Arg/Arg and Gly/Gly.

Throughout the treatment period, patients will be instructed to use ipratropium bromide (Atrovent-HFA), a bronchodilator which works through a different mechanism for rescue therapy; albuterol will be available for use if necessary.

The goal of this study is to determine if the withdrawal of a beta 2 agonist leads to improved asthma control in those asthmatic patients with the Arg/Arg genotype compared with those with the Gly/Gly genotype.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* History of moderate or severe and persistent asthma
* Currently being treated with a long acting beta agonist and inhaled corticosteroid
* Forced expiratory volume at one second (FEV1) \> or = 70% at randomization visit (pulmonary function test result)
* Women of childbearing potential must be on an effective form of contraception
* Ability to read and understand English

Exclusion Criteria:

* Active smoking or greater than 10-pack-year history of smoking
* History of intubation for asthma within the past 10 years
* Patients who are pregnant, become pregnant during the study or are breast feeding
* Major comorbidity including: severe cardiac disease, uncontrolled hypertension, poorly controlled diabetes, malignancy within the past 5 years (except non-melanoma skin lesions), and pulmonary disease other than asthma

Primary outcomes:
measure: Absolute Change in Morning Peak Flow
timeFrame: Up to 16 weeks from baseline
Secondary outcomes:
measure: Change in Forced Expiratory Volume in 1 Second (FEV1) Pre-Bronchodilator
timeFrame: Up to 16 weeks from baseline
measure: Change in Forced Expiratory Volume in 1 Second (FEV1) Post-Bronchodilator
timeFrame: Up to 16 weeks from baseline
measure: Change in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted Pre-Bronchodilator
timeFrame: Up to 16 weeks from baseline
measure: Change in Asthma Symptom Score
timeFrame: Up to 16 weeks from baseline
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center Eastside
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Marjorie Slankard, M.D.
role: PRINCIPAL_INVESTIGATOR
References: