NCT00595361

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable asthma

Timeline
Completed

Started Jan 2008

Longer than P75 for not_applicable asthma

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2008

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

January 7, 2008

Completed
9 days until next milestone

First Posted

Study publicly available on registry

January 16, 2008

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

August 8, 2014

Completed
Last Updated

June 8, 2017

Status Verified

May 1, 2017

Enrollment Period

3.3 years

First QC Date

January 7, 2008

Results QC Date

July 16, 2014

Last Update Submit

May 15, 2017

Conditions

Asthma

Keywords

asthmaexercise induced asthmaexercise induced bronchoconstrictionlong acting beta agonistsalmeterolexercise challengebronchoprotectionbeta 2 adrenergic receptor polymorphismspharmacogenetics

Outcome Measures

Primary Outcomes (1)

  • 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 after exercise challenge

Secondary Outcomes (2)

  • 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 Patients

    2 weeks from pre-salmeterol baseline

  • 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 after 1st dose of Salmeterol

Study Arms (2)

Arg/Arg

ACTIVE COMPARATOR

Arg/Arg subjects on 2 week salmeterol treatment

Drug: salmeterol

Gly/Gly

ACTIVE COMPARATOR

Gly/Gly subjects on 2 week salmeterol treatment

Drug: salmeterol

Interventions

salmeterolDRUG

salmeterol 50 micrograms twice daily for 2 weeks

Arg/ArgGly/Gly

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Both male and female
  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (9)

  • 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. doi: 10.1164/ajrccm.162.1.9907092.

    PMID: 10903223RESULT

  • 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. doi: 10.1016/S0140-6736(04)17273-5.

    PMID: 15500895RESULT

  • 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. doi: 10.1164/rccm.200509-1519OC. Epub 2005 Dec 1.

    PMID: 16322642RESULT

  • 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. doi: 10.1016/0954-6111(94)90042-6.

    PMID: 7913549RESULT

  • 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. doi: 10.1164/ajrccm.156.3.9610051.

    PMID: 9310023RESULT

  • 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.

    PMID: 9664089RESULT

  • 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.

    PMID: 16772309RESULT

  • 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.

    PMID: 15806036RESULT

  • 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.

    PMID: 24228710DERIVED

MeSH Terms

Conditions

AsthmaAsthma, Exercise-Induced

Interventions

Salmeterol Xinafoate

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System DiseasesExercise-Induced Allergies

Intervention Hierarchy (Ancestors)

AlbuterolEthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesPhenethylaminesEthylamines

Results Point of Contact

Title
Elliot Israel, MD
Organization
Brigham and Women's Hopsital
eisrael@partners.org
617-732-8110

Study Officials

  • Elliot Israel, M.D.

    Asthma Research Center, Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director, Asthma Research Center

Study Record Dates

First Submitted

January 7, 2008

First Posted

January 16, 2008

Study Start

January 1, 2008

Primary Completion

May 1, 2011

Study Completion

March 1, 2012

Last Updated

June 8, 2017

Results First Posted

August 8, 2014

Record last verified: 2017-05

Locations

US(2)