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

Asthma Clinical Trial

— SECS  

Official title:

The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00595361
• Other study ID #: 2007-P-002199
• Status: Completed
• Phase: N/A
• First received: January 7, 2008
• Last updated: September 21, 2015
• Start date: January 2008
• Est. completion date: March 2012

Study information

• Verified date: September 2015
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2012
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• salmeterol
salmeterol 50 micrograms twice daily for 2 weeks

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (8)

Israel E, Chinchilli VM, Ford JG, Boushey HA, Cherniack R, Craig TJ, Deykin A, Fagan JK, Fahy JV, Fish J, Kraft M, Kunselman SJ, Lazarus SC, Lemanske RF Jr, Liggett SB, Martin RJ, Mitra N, Peters SP, Silverman E, Sorkness CA, Szefler SJ, Wechsler ME, Weis — View Citation

Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, Cooper DM, Fahy JV, Fish JE, Ford JG, Kraft M, Kunselman S, Lazarus SC, Lemanske RF, Martin RJ, McLean DE, Peters SP, Silverman EK, Sorkness CA, Szefler SJ, Weiss ST, Yandava CN. Th — View Citation

Israel E. Genetics and the variability of treatment response in asthma. J Allergy Clin Immunol. 2005 Apr;115(4 Suppl):S532-8. Review. — View Citation

Nelson JA, Strauss L, Skowronski M, Ciufo R, Novak R, McFadden ER Jr. Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med. 1998 Jul 16;339(3):141-6. — View Citation

Palmer CN, Lipworth BJ, Lee S, Ismail T, Macgregor DF, Mukhopadhyay S. Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol. Thorax. 2006 Nov;61(11):940-4. Epub 2006 Jun 13. — View Citation

Ramage L, Lipworth BJ, Ingram CG, Cree IA, Dhillon DP. Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol. Respir Med. 1994 May;88(5):363-8. — View Citation

Wechsler ME, Lehman E, Lazarus SC, Lemanske RF Jr, Boushey HA, Deykin A, Fahy JV, Sorkness CA, Chinchilli VM, Craig TJ, DiMango E, Kraft M, Leone F, Martin RJ, Peters SP, Szefler SJ, Liu W, Israel E; National Heart, Lung, and Blood Institute's Asthma Clin — View Citation

Yates DH, Worsdell M, Barnes PJ. Effect of regular salmeterol treatment on albuterol-induced bronchoprotection in mild asthma. Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):988-91. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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		2 weeks	Yes
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 Subjects		2 weeks	Yes
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		2 weeks	Yes