Asthma
Conditions
Keywords
asthma, exercise induced asthma, exercise induced bronchoconstriction, long acting beta agonist, salmeterol, exercise challenge, bronchoprotection, beta 2 adrenergic receptor polymorphisms, pharmacogenetics
Brief summary
The purpose of the study is to find out how well a long-acting beta agonist like salmeterol works in people with different forms of the same gene. Our hypothesis is that asthmatics with the Arg/Arg genotype will have loss of bronchoprotection against exercise-induced asthma with regular salmeterol treatment, as compared to asthmatics with the Gly/Gly genotype.
Detailed description
In many patients with asthma, exercise-induced bronchoconstriction is a common and oftentimes limiting characteristic. Inhaled β2-adrenoreceptor agonists like albuterol are the most effective treatments available for the relief of acute asthma symptoms. However, there is evidence that regular use may lead to adverse effects in some patients. Previous studies have shown that polymorphisms of the β2-adrenergic receptor can influence airway responses to regular inhaled beta-agonist treatment. Pharmacogenetics is the study of how genetic differences influence the variability in patients' responses to therapy, both therapeutic and adverse. Genetic susceptibility and environmental factors both play major roles in the etiology of asthma. The strong familial clustering of asthma has lead to a surge of research into the genetic predisposition of asthma. The aim of the present study is to utilize a double-blinded prospective cohort study to investigate whether genotype-specific effects occur when assessing the duration of protection conferred against exercise-induced bronchoconstriction by regular salmeterol treatment.
Interventions
DRUGsalmeterol
salmeterol 50 micrograms twice daily for 2 weeks
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Both male and female * 18 to 50 years of age * Resting FEV1 ≥ 65% of predicted normal * Exercise-induced bronchoconstriction defined as a decrease in FEV1 of ≥ 20% following a standardized exercise challenge when compared to pre-exercise baseline FEV1 value measured 5 minutes before exercise * Must be Arg/Arg or Gly/Gly genotype
Exclusion criteria
* Long-acting beta agonist use within 12 weeks of the first exercise challenge * Smoking within past 12 months * Greater than 10-pack years smoking history * Unresolved signs and/or symptoms of an upper respiratory tract infection within 4 weeks of first exercise challenge * Asthma exacerbation within 4 weeks of first exercise challenge requiring change in type, dose or frequency of medications and/or an unscheduled visit to an health care provider, including emergency room or hospital * Subject has exercised or performed strenuous activity within 72 hours of the first exercise challenge * Subject has been exposed to cold air sufficient to provoke symptoms of bronchospasm within 2 hours of exercise challenge * In addition to asthma, the subject has an active, acute or chronic pulmonary disorder documented by history, physical examination, or chest x-ray * Subject has evidence of ischemic, valvular, hypertrophic, familial or other forms of heart disease that would put the subject at risk during exercise testing or that would interfere with the ability to achieve protocol-specified heart rates during exercise testing * Subject has used systemic corticosteroids within 1 month of first exercise challenge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of the Maximum Percent Fall in FEV1 After Exercise Challenge at the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 2 weeks after exercise challenge |
Secondary
| Measure | Time frame |
|---|---|
| Comparison of the Maximum Percent Fall in FEV1 From Pre-salmeterol Baseline to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 2 weeks from pre-salmeterol baseline |
| Comparison of the Maximum Percent Fall in FEV1 After 1st Dose of Salmeterol to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Subjects | 2 weeks after 1st dose of Salmeterol |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arg/Arg Arg/Arg subjects on 2 week salmeterol treatment
salmeterol: salmeterol 50 micrograms twice daily for 2 weeks | 12 |
| Gly/Gly Gly/Gly subjects on 2 week salmeterol treatment
salmeterol: salmeterol 50 micrograms twice daily for 2 weeks | 14 |
| Total | 26 |
Baseline characteristics
| Characteristic | Arg/Arg | Gly/Gly | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 14 Participants | 26 Participants |
| Age, Continuous | 25.8 years STANDARD_DEVIATION 2.4 | 27.2 years STANDARD_DEVIATION 1.4 | 26.6 years STANDARD_DEVIATION 1.3 |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 14 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 |
Outcome results
Primary
Comparison of the Maximum Percent Fall in FEV1 After Exercise Challenge at the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients
Time frame: 2 weeks after exercise challenge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arg/Arg | Comparison of the Maximum Percent Fall in FEV1 After Exercise Challenge at the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 12.6 % fall FEV1 | Standard Deviation 4.5 |
| Gly/Gly | Comparison of the Maximum Percent Fall in FEV1 After Exercise Challenge at the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 16.5 % fall FEV1 | Standard Deviation 2.9 |
Secondary
Comparison of the Maximum Percent Fall in FEV1 After 1st Dose of Salmeterol to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Subjects
Time frame: 2 weeks after 1st dose of Salmeterol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arg/Arg | Comparison of the Maximum Percent Fall in FEV1 After 1st Dose of Salmeterol to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Subjects | -12.6 % fall FEV1 | Standard Deviation 17.1 |
| Gly/Gly | Comparison of the Maximum Percent Fall in FEV1 After 1st Dose of Salmeterol to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Subjects | -16.5 % fall FEV1 | Standard Deviation 10.9 |
Secondary
Comparison of the Maximum Percent Fall in FEV1 From Pre-salmeterol Baseline to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients
Time frame: 2 weeks from pre-salmeterol baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arg/Arg | Comparison of the Maximum Percent Fall in FEV1 From Pre-salmeterol Baseline to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 5.9 % fall FEV1 | Standard Deviation 19.9 |
| Gly/Gly | Comparison of the Maximum Percent Fall in FEV1 From Pre-salmeterol Baseline to the End of the 2-week Treatment Period Between Arg/Arg and Gly/Gly Patients | 4.3 % fall FEV1 | Standard Deviation 10.6 |