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

This study has been terminated.
(Funding was terminated)
Sponsor:
Collaborators:
Baim Institute for Clinical Research
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: May 5, 2017
Last verified: May 2017
  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 Drug: Formoterol Drug: Fluticasone propionate Drug: budesonide

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Genotype Stratified Treatment With Anticholinergic vs. Beta-agonist (Long Acting) and Exacerbations (GABLE)

Further study details as provided by Elliot Israel, MD, Brigham and Women's Hospital:

Primary Outcome Measures:
  • Number of Patients With Asthma Exacerbation [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • FEV1 (Forced Expiratory Volume) [ Time Frame: 1 year ]
  • Exhaled NO (Nitric Oxide) [ Time Frame: 1 year ]
  • Symptom-free Days [ Time Frame: 1 year ]
  • Asthma-related Quality of Life [ Time Frame: 1 year ]

Enrollment: 255
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 - Tio/ICS in the Arg/Arg genotype
Tiotropium bromide 18 mcg qd plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, 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
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler
Experimental: 2 - Tio/ICS in the Arg/Gly genotype
Tiotropium bromide 18 mcg QD plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, 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
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler
Experimental: 3 - Tio/ICS in the Gly/Gly genotype
Tiotropium bromide 18 mcg QD plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, 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
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler
Active Comparator: 4 - LABA/ICS in the Arg/Arg genotype
Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Arg genotype
Drug: Salmeterol
salmeterol diskus 1 puff 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 Name: Serevent
Drug: Formoterol
formoterol aerolizer 12 mcg 1 puff 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 Name: Foradil
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler
Active Comparator: 5 - LABA/ICS in the Arg/Gly genotype
Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Gly genotype
Drug: Salmeterol
salmeterol diskus 1 puff 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 Name: Serevent
Drug: Formoterol
formoterol aerolizer 12 mcg 1 puff 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 Name: Foradil
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler
Active Comparator: 6 - LABA/ICS in the Gly/Gly genotype
Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Gly-Gly genotype
Drug: Salmeterol
salmeterol diskus 1 puff 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 Name: Serevent
Drug: Formoterol
formoterol aerolizer 12 mcg 1 puff 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 Name: Foradil
Drug: Fluticasone propionate
Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Flovent
Drug: budesonide
Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.
Other Name: Pulmicort Flexihaler

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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

Additional Information:
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
Results First Received: March 17, 2017
Last Updated: May 5, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Elliot Israel, MD, 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
Fluticasone
Budesonide
Tiotropium Bromide
Salmeterol Xinafoate
Formoterol Fumarate
Bromides
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
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants

ClinicalTrials.gov processed this record on June 23, 2017