Study of the Effects of Different Long-acting Bronchodilator Medications on Asthma Patients With Different Genetic Variations (GABLE)

This study has been terminated.
Sponsor:
Collaborators:
Harvard Clinical Research Institute
Massachusetts General Hospital
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00706446
First received: June 25, 2008
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

This study is looking at the effects of certain long-acting bronchodilators on patients with asthma who have specific genetic variations. The investigators 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. The investigators 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.


Condition Intervention
Asthma
Drug: tiotropium bromide
Drug: salmeterol or formoterol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Genotype Stratified Treatment With Anticholinergic vs. Beta-agonist (Long Acting) and Exacerbations (GABLE)

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Asthma exacerbations [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • FEV1 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Exhaled NO [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Symptom-free days [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Asthma-related Quality of Life [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 355
Study Start Date: June 2008
Study Completion Date: September 2011
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Tiotropium bromide plus inhaled steroids in the Arg/Arg genotype
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.
Other Name: Spiriva
Experimental: 2
Tiotropium bromide plus inhaled steroids in the Arg/Gly genotype
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.
Other Name: Spiriva
Experimental: 3
Tiotropium bromide plus inhaled steroid in the Gly/Gly genotype
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.
Other Name: Spiriva
Active Comparator: 4
Salmeterol or Formoterol plus inhaled steroid in the Arg/Arg genotype
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.
Other Names:
  • Serevent
  • Foradil
  • Advair
  • Symbicort
Active Comparator: 5
Salmeterol or Formoterol plus inhaled steroid in the Arg-Gly genotype
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.
Other Names:
  • Serevent
  • Foradil
  • Advair
  • Symbicort
Active Comparator: 6
Salmeterol or Formoterol plus inhaled steroid in the Gly-Gly genotype
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.
Other Names:
  • Serevent
  • Foradil
  • Advair
  • Symbicort

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00706446

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Brigham and Women's Hospital
Harvard Clinical Research Institute
Massachusetts General Hospital
Investigators
Principal Investigator: Elliot Israel, MD Brigham and Women's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Elliot Israel, MD, Director of the Asthma Research Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00706446     History of Changes
Other Study ID Numbers: 2008-P-000285
Study First Received: June 25, 2008
Last Updated: August 5, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
Asthma
Pharmacogenetics
Beta agonists
salmeterol
formoterol
tiotropium
beta adrenergic receptor
single nucleotide polymorphism

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bromides
Formoterol
Salmeterol
Tiotropium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics

ClinicalTrials.gov processed this record on April 17, 2014