How Different Beta-2 Receptor Genotypes Affect an Asthmatic's Response to Regular Salmeterol Treatment (SECS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Elliot Israel, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00595361
First received: January 7, 2008
Last updated: July 16, 2014
Last verified: July 2014

January 7, 2008
July 16, 2014
January 2008
May 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
comparison of maximum percent fall in FEV1 from pre-exercise baseline after each exercise challenge between Arg/Arg and Gly/Gly patients [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00595361 on ClinicalTrials.gov Archive Site
  • 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 Subjects [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
comparisons of the maximum percent fall in FEV1 from pre-exercise baseline between the 3 exercise challenges within each group [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
How Different Beta-2 Receptor Genotypes Affect an Asthmatic's Response to Regular Salmeterol Treatment
The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Asthma
Drug: salmeterol
salmeterol 50 micrograms twice daily for 2 weeks
  • Active Comparator: Arg/Arg
    Arg/Arg subjects on 2 week salmeterol treatment
    Intervention: Drug: salmeterol
  • Active Comparator: Gly/Gly
    Gly/Gly subjects on 2 week salmeterol treatment
    Intervention: Drug: salmeterol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
March 2012
May 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 50 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00595361
2007-P-002199
Yes
Elliot Israel, MD, Brigham and Women's Hospital
Brigham and Women's Hospital
Not Provided
Principal Investigator: Elliot Israel, M.D. Asthma Research Center, Brigham and Women's Hospital
Brigham and Women's Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP