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. 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:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Asthma

Drug Information available for: Formoterol fumarate Arformoterol Formoterol Salmeterol Salmeterol xinafoate Advair Tiotropium bromide Symbicort 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:	August 2011
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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. Other Name: Spiriva
Experimental: 2 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. Other Name: Spiriva
Experimental: 3 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. Other Name: Spiriva
Active Comparator: 4 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. Other Names: Serevent Foradil Advair Symbicort
Active Comparator: 5 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. Other Names: Serevent Foradil Advair Symbicort
Active Comparator: 6 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. 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:

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

No publications provided

Responsible Party:	Elliot Israel, MD, 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:	July 11, 2011
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 February 09, 2012