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
  Purpose

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.


Condition Intervention
Asthma
Drug: salmeterol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: January 2008
Study Completion Date: March 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arg/Arg
Arg/Arg subjects on 2 week salmeterol treatment
Drug: salmeterol
salmeterol 50 micrograms twice daily for 2 weeks
Active Comparator: Gly/Gly
Gly/Gly subjects on 2 week salmeterol treatment
Drug: salmeterol
salmeterol 50 micrograms twice daily for 2 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00595361

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Elliot Israel, M.D. Asthma Research Center, Brigham and Women's Hospital
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Elliot Israel, MD, Director, Asthma Research Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00595361     History of Changes
Other Study ID Numbers: 2007-P-002199
Study First Received: January 7, 2008
Results First Received: July 16, 2014
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
asthma
exercise induced asthma
exercise induced bronchoconstriction
long acting beta agonist
salmeterol
exercise challenge
bronchoprotection
beta 2 adrenergic receptor polymorphisms
pharmacogenetics

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Salmeterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014