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

NCT ID: NCT00595361

Last Updated: 2017-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2012-03-31

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.

Conditions

Asthma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arg/Arg

Arg/Arg subjects on 2 week salmeterol treatment

Group Type: ACTIVE_COMPARATOR

salmeterol

Intervention Type: DRUG

salmeterol 50 micrograms twice daily for 2 weeks

Gly/Gly

Gly/Gly subjects on 2 week salmeterol treatment

Group Type: ACTIVE_COMPARATOR

salmeterol

Intervention Type: DRUG

salmeterol 50 micrograms twice daily for 2 weeks

Interventions

salmeterol

salmeterol 50 micrograms twice daily for 2 weeks

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elliot Israel, MD

Director, Asthma Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elliot Israel, M.D.

Role: PRINCIPAL_INVESTIGATOR

Asthma Research Center, Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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Reference Type: RESULT

PMID: 10903223 (View on PubMed)

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

PMID: 9310023 (View on PubMed)

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. doi: 10.1056/NEJM199807163390301.

Reference Type: RESULT

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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. doi: 10.1136/thx.2006.059386. Epub 2006 Jun 13.

Reference Type: RESULT

PMID: 16772309 (View on PubMed)

Israel E. Genetics and the variability of treatment response in asthma. J Allergy Clin Immunol. 2005 Apr;115(4 Suppl):S532-8. doi: 10.1016/j.jaci.2005.01.029.

Reference Type: RESULT

PMID: 15806036 (View on PubMed)

Bonini M, Permaul P, Kulkarni T, Kazani S, Segal A, Sorkness CA, Wechsler ME, Israel E. Loss of salmeterol bronchoprotection against exercise in relation to ADRB2 Arg16Gly polymorphism and exhaled nitric oxide. Am J Respir Crit Care Med. 2013 Dec 15;188(12):1407-12. doi: 10.1164/rccm.201307-1323OC.

Reference Type: DERIVED

PMID: 24228710 (View on PubMed)

Other Identifiers

2007-P-002199

Identifier Type: -

Identifier Source: org_study_id