Official Title: “Genotype Stratified Treatment With Anticholinergic vs. Beta-Agonist (Long Acting) and Exacerbations (GABLE)”

This study is looking at the effects of certain long-acting bronchodilators on patients with asthma who have specific genetic variations. We are interested in a certain common genetic variation in the receptor for beta-agonists, which is found in as many of one-sixth of the population. There is evidence that patients with asthma who have this variation may not do as well when treated with albuterol on a regular basis. We will be looking at whether patients with this variation have more asthma exacerbations over the course of a year when treated with salmeterol or formoterol, which are long-acting forms of albuterol; and whether these patients have fewer exacerbations when treated with tiotropium, which is a different long-acting bronchodilator that does not act at this receptor. In both groups patients will also be receiving inhaled steroids.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2010

Intervention(s) in this Clinical Trial

• Drug: tiotropium bromide
  • tiotropium bromide one inhalation a day for one year, along with inhaled steroids at variable dosing based on patient's prior inhaled steroid dosing and treating physician's judgement.
• Drug: salmeterol or formoterol
  • salmeterol diskus 1 puff twice a day or formoterol inhaler 2 puffs twice a day for 1 year, depending on which medication the patient was on before the start of the trial. The goal of this intervention is to continue the patient's current therapy of long-acting beta-agonists. In addition, the patients will be on inhaled steroids at variable doses, depending on what dose they were on at the start of the trial and based on the judgement of their treating physicians.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Tiotropium plus inhaled steroids in the Arg/Arg genotype
• Experimental: 2
  • Tiotropium plus inhaled steroids in the Arg/Gly genotype
• Experimental: 3
  • Tiotropium plus inhaled steroid in the Gly/Gly genotype
• Active Comparator: 4
  • Long-acting beta agonist plus inhaled steroid in the Arg/Arg genotype
• Active Comparator: 5
  • Long-acting beta agonist plus inhaled steroid in the Arg-Gly genotype
• Active Comparator: 6
  • Long-acting beta agonist plus inhaled steroid in the Gly-Gly genotype

Primary Measures

• Asthma exacerbations
  • Time Frame: 1 year
    Safety Issue?: No

Secondary Measures

• FEV1
  • Time Frame: 1 year
    Safety Issue?: No
• Exhaled NO
  • Time Frame: 1 year
    Safety Issue?: No
• Symptom-free days
  • Time Frame: 1 year
    Safety Issue?: No
• Asthma-related Quality of Life
  • Time Frame: 1 year
    Safety Issue?: No

Inclusion Criteria:

• Clinical history consistent with asthma
• Has a current prescription for a long-acting beta agonist, either along or in combination with an inhaled corticosteroid (salmeterol, formoterol, fluticasone/salmeterol, or budesonide/formoterol)
• Ability to provide informed consent
• Non-smoker (total lifetime smoking history < 10 pack-years; no more than five occasions of smoking any substance or using smokeless tobacco products in the past year)
• No smoking or use of smokeless tobacco in the past 30 days
• No known contraindication to inhaled tiotropium e.g. narrow angle glaucoma, history of bladder neck obstruction or significant symptoms related to prostatic hypertrophy.

Exclusion Criteria:

• Lung disease other than asthma
• Established or suspected diagnosis of vocal cord dysfunction
• Significant medical illness (other than asthma) that is not stable
• History of life-threatening asthma requiring treatment with intubation and mechanical ventilation within the past 5 years
• History of respiratory tract infection within the previous 4 weeks (only applies at screening visits)
• Hyposensitization therapy other than an established maintenance regimen
• Allergy to tiotropium
• Pregnancy or lactation. If potentially able to bear children, not using an acceptable form of birth control.
• Inability to use inhaler devices.
• Inability to participate over the one year period
• Current use of tiotropium.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Brigham and Women's Hospital

Overall Clinical Trial Officials and Contacts

Elliot Israel, MD Principal Investigator Brigham and Women's Hospital  

Overall Contact: Stefanie Dutile 617-732-8266 

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00706446

Study ID Number: 2008-P-000285

ClinicalTrials.gov Identifier: NCT00706446

Health Authority: United States: Food and Drug Administration

Brigham and Women's Hospital Asthma Research Center