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

NCT ID: NCT00521222

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-06-30
• Study Completion Date: 2010-11-30

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Fluticasone with salmeterol

Intervention Type: DRUG

Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period.

Ipratropium HFA

Intervention Type: DRUG

Primary as-needed rescue medication in all treatment groups

Albuterol HFA

Intervention Type: DRUG

Secondary as-needed rescue medication in all treatment groups

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.

Group Type: ACTIVE_COMPARATOR

Fluticasone with salmeterol

Intervention Type: DRUG

Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period.

Ipratropium HFA

Intervention Type: DRUG

Primary as-needed rescue medication in all treatment groups

Albuterol HFA

Intervention Type: DRUG

Secondary as-needed rescue medication in all treatment groups

Arg/Arg genotype on Fluticasone HFA

Asthma patients with the Arg/Arg genotype who are randomized to fluticasone (Flovent HFA) alone.

Group Type: EXPERIMENTAL

Fluticasone HFA

Intervention Type: DRUG

Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period.

Ipratropium HFA

Intervention Type: DRUG

Primary as-needed rescue medication in all treatment groups

Albuterol HFA

Intervention Type: DRUG

Secondary as-needed rescue medication in all treatment groups

Gly/Gly genotype on Fluticasone HFA

Asthma patients with the Gly/Gly genotype who are randomized to fluticasone (Flovent HFA) alone.

Group Type: EXPERIMENTAL

Fluticasone HFA

Intervention Type: DRUG

Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period.

Ipratropium HFA

Intervention Type: DRUG

Primary as-needed rescue medication in all treatment groups

Albuterol HFA

Intervention Type: DRUG

Secondary as-needed rescue medication in all treatment groups

Interventions

Fluticasone with salmeterol

Fluticasone 45mcg, 115mcg, or 230mcg with salmeterol 21mcg, via HFA device, 2 puffs every 12 hrs, over 16 week study period.

Intervention Type: DRUG

Fluticasone HFA

Fluticasone HFA alone at 44mcg, 110mcg or 220 mcg 2 puffs every 12 hrs, over 16 week study period.

Intervention Type: DRUG

Ipratropium HFA

Primary as-needed rescue medication in all treatment groups

Intervention Type: DRUG

Albuterol HFA

Secondary as-needed rescue medication in all treatment groups

Intervention Type: DRUG

Other Intervention Names

Advair HFA; Flovent HFA; Atrovent

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marjorie Slankard, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University Medical Center Eastside

New York, New York, United States

Columbia Presbyterian Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAC1135

Identifier Type: -

Identifier Source: org_study_id