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

Study Description

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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	Not Applicable

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

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Study Type :	Interventional (Clinical Trial)
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 :	June 2007
Actual Primary Completion Date :	November 2010
Estimated Study Completion Date :	November 2013

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: 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 Name: 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 Name: Flovent HFA

Outcome Measures

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Primary Outcome Measures :

1. Absolute change in morning peak flow [ Time Frame: 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 :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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
• 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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center Eastside
New York, New York, United States, 10022
Columbia Presbyterian Medical Center
New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

Principal Investigator:	Marjorie Slankard, M.D.	Columbia University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Marjorie Slankard, Clinical Professor of Medicine, Pulmonary, Columbia University
ClinicalTrials.gov Identifier:	NCT00521222 History of Changes
Other Study ID Numbers:	AAAC1135
First Posted:	August 27, 2007
Last Update Posted:	June 11, 2013
Last Verified:	June 2013

Keywords provided by Marjorie Slankard, Columbia University:

asthma; beta agonist; bronchodilator; pulmonary; genotype	pharmacogenomics; corticosteroid; allergy; immunology

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Salmeterol Xinafoate; Fluticasone Propionate, Salmeterol Xinafoate Drug Combination; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents

Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists