Study of the Effects of Different Long-acting Bronchodilator Medications on Asthma Patients With Different Genetic Variations - Full Text View

Sponsor:	Brigham and Women's Hospital
Collaborators:	Harvard Clinical Research Institute Massachusetts General Hospital
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00706446

Purpose

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.

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

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Genotype Stratified Treatment With Anticholinergic vs. Beta-agonist (Long Acting) and Exacerbations (GABLE)

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Asthma

Drug Information available for: Formoterol fumarate Arformoterol Formoterol Salmeterol Salmeterol xinafoate Tiotropium bromide Tiotropium Arformoterol Tartrate

U.S. FDA Resources

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 ]

Estimated Enrollment:	438
Study Start Date:	June 2008
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Tiotropium 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.
2: Experimental Tiotropium 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.
3: Experimental Tiotropium 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.
4: Active Comparator Long-acting beta agonist 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.
5: Active Comparator Long-acting beta agonist 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.
6: Active Comparator Long-acting beta agonist 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.

Eligibility

Ages Eligible for Study:	18 Years to 70 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

Contacts

Contact: Stefanie Dutile

617-732-8266

Locations

United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Principal Investigator: Elliot Israel, MD
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Fiona Gibbons, MD

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:

Brigham and Women's Hospital Asthma Research Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Brigham and Women's Hospital ( Elliot Israel, MD )
Study ID Numbers:	2008-P-000285
Study First Received:	June 25, 2008
Last Updated:	September 15, 2009
ClinicalTrials.gov Identifier:	NCT00706446 History of Changes
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:

Parasympatholytics
Respiratory System Agents
Neurotransmitter Agents
Cholinergic Antagonists
Bronchial Diseases
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinergic Agents
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Bromides
Therapeutic Uses

Formoterol
Tiotropium
Salmeterol
Immune System Diseases
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Asthma
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Central Nervous System Agents
Bronchodilator Agents
Anticonvulsants

ClinicalTrials.gov processed this record on February 08, 2010