AsthmaSECSNCT00595361
How Different Beta-2 Receptor Genotypes Affect an Asthmatic's Response to Regular Salmeterol Treatment
A study testing salmeterol in people with Asthma, run by Brigham and Women's Hospital at 2 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Asthma
- What is being tested?
- salmeterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2008to Mar 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Wisconsin
Madison, Wisconsin, 53792
About this study
Official title: The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma
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.
Read the 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
- Being tested
- salmeterol
- Keywords
- asthma, exercise induced asthma, exercise induced bronchoconstriction, long acting beta agonist, salmeterol, exercise challenge, bronchoprotection, beta 2 adrenergic receptor polymorphisms, pharmacogenetics
- Medical subject headings
- Asthma, Asthma, Exercise-Induced
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
salmeterolDrug
salmeterol 50 micrograms twice daily for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arg/Arg | Active comparator | Arg/Arg subjects on 2 week salmeterol treatment Receives: Drug: salmeterol |
| Gly/Gly | Active comparator | Gly/Gly subjects on 2 week salmeterol treatment Receives: Drug: salmeterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 2 weeks after 1st dose of Salmeterol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2008 (estimated)
- Study startJan 2008
- Primary completionMay 2011
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elliot Israel, MD, Brigham and Women's Hospital
- Investigators
- Elliot Israel, M.D., Principal investigator, Asthma Research Center, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00595361
- Sponsor's protocol ID
- 2007-P-002199
- Acronym
- SECS
- Status last verified
- May 2017
- First submitted
- 7 Jan 2008
- Last updated
- 8 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 10903223Israel 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.
PubMed 15500895Wechsler 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.
PubMed 16322642Ramage 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.
PubMed 7913549Yates 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.
PubMed 9310023Nelson 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.
PubMed 9664089Palmer 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.
PubMed 16772309Israel 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.
PubMed 15806036Bonini 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.
PubMed 24228710
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma
- ClinicalTrials.gov ID
- NCT00595361
- Acronym / sponsor ID
- SECS / 2007-P-002199
- Conditions
- Asthma
- Keywords
- asthma, exercise induced asthma, exercise induced bronchoconstriction, long acting beta agonist, salmeterol, exercise challenge, bronchoprotection, beta 2 adrenergic receptor polymorphisms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- May 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 16 Jan 2008 (estimated)
- Results
- Posted 8 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arg/Arg | Active comparator | Drug: salmeterolArg/Arg subjects on 2 week salmeterol treatment |
| Gly/Gly | Active comparator | Drug: salmeterolGly/Gly subjects on 2 week salmeterol treatment |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| salmeterolsalmeterol 50 micrograms twice daily for 2 weeks | Drug | Arg/Arg, Gly/Gly |
Primary outcome
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 after exercise challenge
2 secondary outcomes
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
Time frame: 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
Time frame: 2 weeks after 1st dose of Salmeterol
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 10903223Israel 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.
- Results publication: PubMed 15500895Israel 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.
- Results publication: PubMed 16322642Wechsler 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.
- Results publication: PubMed 7913549Ramage 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.
- Results publication: PubMed 9310023Yates 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.
- Results publication: PubMed 9664089Nelson 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.
- Results publication: PubMed 16772309Palmer 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.
- Results publication: PubMed 15806036Israel 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.
- Derived from this study: PubMed 24228710Bonini 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elliot Israel, M.D. principal investigator
Asthma Research Center, Brigham and Women's Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing salmeterol in people with Asthma, run by Brigham and Women's Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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 after exercise challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00595361, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017; AzTrials last refreshed its copy on 29 Oct 2026.