Expired Study
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Madison, Wisconsin 53792


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.


Study summary:

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.


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


Study is Available At:


Original ID:

2007-P-002199


NCT ID:

NCT00595361


Secondary ID:


Study Acronym:

SECS


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

N/A


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

50 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Brigham and Women's Hospital


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Non-Randomized, Endpoint Classificatio


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

30


Enrollment Type:

Actual


Overall Contact Information

Official Name:Elliot Israel, M.D.
Principal Investigator
Asthma Research Center, Brigham and Women's Hospital

Study Dates

Start Date:January 2008
Completion Date:March 2012
Completion Type:Actual
Primary Completion Date:May 2011
Primary Completion Type:Actual
Verification Date:September 2015
Last Changed Date:September 21, 2015
First Received Date:January 7, 2008
First Results Date:July 16, 2014

Study Outcomes

Outcome Type:Secondary Outcome
Measure: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
Safety Issues:True
Outcome Type:Secondary Outcome
Measure: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
Safety Issues:True
Outcome Type: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
Safety Issues:True

Study Interventions

Intervention Type:Drug
Name:salmeterol
Description:salmeterol 50 micrograms twice daily for 2 weeks
Arm Name:Arg/Arg

Study Arms

Study Arm Type:Active Comparator
Arm Name:Gly/Gly
Description:Gly/Gly subjects on 2 week salmeterol treatment
Study Arm Type:Active Comparator
Arm Name:Arg/Arg
Description:Arg/Arg subjects on 2 week salmeterol treatment

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Brigham and Women's Hospital

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Israel E. Genetics and the variability of treatment response in asthma. J Allergy Clin Immunol. 2005 Apr;115(4 Suppl):S532-8. Review.
PMID:15806036
Reference Type:Results Reference
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.
PMID:16772309
Reference Type:Results Reference
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.
PMID:9664089
Reference Type:Results Reference
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.
PMID:9310023
Reference Type:Results Reference
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.
PMID:7913549
Reference Type:Results Reference
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 Clinical Research Network. beta-Adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care Med. 2006 Mar 1;173(5):519-26. Epub 2005 Dec 1.
PMID:16322642
Reference Type:Results Reference
Citation: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, Weiss ST, Drazen JM; National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004 Oct 23-29;364(9444):1505-12.
PMID:15500895
Reference Type:Results Reference
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. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000 Jul;162(1):75-80.
PMID:10903223

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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