ARGARG: Evaluating Long Acting Beta Agonists Used to Treat Asthma Among Those With Either Arg/Arg or Gly/Gly Genotypes

Sponsor

Columbia University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00521222

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

29.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone with salmeterol Drug: Fluticasone HFA	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

89 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Arg/Arg Genotype and Long Acting Beta Agonists in Asthma. Improved Quality of Care for Patients With Asthma.

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Nov 1, 2010

Anticipated Study Completion Date :

Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arg/Arg genotype on Advair (Fluticasone with Salmeterol) HFA Asthma patients with the Arg/Arg genotype who are randomized to continue the combination therapy of a specific long-acting beta 2 agonist (salmeterol) and inhaled corticosteroid (fluticasone) in the form of Advair HFA.	Drug: Fluticasone with salmeterol Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period. Other Names: Advair HFA
Active Comparator: Gly/Gly genotype on Advair (Fluticasone with Salmeterol) HFA Asthma patients with the Gly/Gly genotype who are randomized to continue the combination therapy of a specific long-acting beta 2 agonist (salmeterol) and inhaled corticosteroid (fluticasone) in the form of Advair HFA.	Drug: Fluticasone with salmeterol Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period. Other Names: Advair HFA
Experimental: Arg/Arg genotype on Fluticasone HFA Asthma patients with the Arg/Arg genotype who are randomized to fluticasone (Flovent HFA) alone.	Drug: Fluticasone HFA Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period. Other Names: Flovent HFA
Experimental: Gly/Gly genotype on Fluticasone HFA Asthma patients with the Gly/Gly genotype who are randomized to fluticasone (Flovent HFA) alone.	Drug: Fluticasone HFA Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period. Other Names: Flovent HFA

Outcome Measures

Primary Outcome Measures

Absolute change in morning peak flow [Up to 16 weeks from baseline]
Absolute change in morning peak flow at the end of the 16-week study period compared with baseline (last two weeks of run-in).

Secondary Outcome Measures

Absolute and percentage change in rescue inhaler use [Up to 16 weeks from baseline]
Outcome will be assessed at the end of the 16 week study period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
2	Columbia University Medical Center Eastside	New York	New York	United States	10022
3	Columbia Presbyterian Medical Center	New York	New York	United States	10032