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

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00595361
• Collaborator: (none)
• Enrollment: 30
• Locations: 2
• Arms: 2
• Duration (Months): 50
• Patients Per Site: 15
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: salmeterol	N/A

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

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Beta-2 Adrenergic Polymorphisms on the Bronchoprotective Effects of Regular Salmeterol Treatment in Asthma
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arg/Arg Arg/Arg subjects on 2 week salmeterol treatment	Drug: salmeterol; salmeterol 50 micrograms twice daily for 2 weeks
Active Comparator: Gly/Gly Gly/Gly subjects on 2 week salmeterol treatment	Drug: salmeterol; salmeterol 50 micrograms twice daily for 2 weeks

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. 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]

2. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	University of Wisconsin	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elliot Israel, MD, Director, Asthma Research Center, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00595361
• Other Study ID Numbers: 2007-P-002199
• First Posted: Jan 16, 2008
• Last Update Posted: Jun 8, 2017
• Last Verified: May 1, 2017

• Keywords provided by Elliot Israel, MD, Director, Asthma Research Center, Brigham and Women's Hospital: asthma; exercise induced asthma; exercise induced bronchoconstriction; long acting beta agonist; salmeterol; exercise challenge; bronchoprotection; beta 2 adrenergic receptor polymorphisms; pharmacogenetics
• Additional relevant MeSH terms: Asthma; Salmeterol Xinafoate

Study Results

Participant Flow

Arm/Group Title	Arg/Arg	Gly/Gly
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks
Period Title: Overall Study
STARTED	12	18
COMPLETED	12	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arg/Arg	Gly/Gly	Total
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Total of all reporting groups
Overall Participants	12	14	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.8 (2.4)	27.2 (1.4)	26.6 (1.3)
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	14 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 83.3%	10 71.4%	20 76.9%
Male	2 16.7%	4 28.6%	6 23.1%
Region of Enrollment (participants) [Number]
United States	12 100%	14 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arg/Arg	Gly/Gly
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks
Measure Participants	12	14
Mean (Standard Deviation) [% fall FEV1]	12.6 (4.5)	16.5 (2.9)

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arg/Arg	Gly/Gly
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks
Measure Participants	12	14
Mean (Standard Deviation) [% fall FEV1]	5.9 (19.9)	4.3 (10.6)

3. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arg/Arg	Gly/Gly
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks	Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks
Measure Participants	12	14
Mean (Standard Deviation) [% fall FEV1]	-12.6 (17.1)	-16.5 (10.9)

Adverse Events

Arm/Group Title	Arg/Arg		Gly/Gly
Arm/Group Description	Arg/Arg subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks		Gly/Gly subjects on 2 week salmeterol treatment salmeterol: salmeterol 50 micrograms twice daily for 2 weeks
All Cause Mortality
	Arg/Arg		Gly/Gly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arg/Arg		Gly/Gly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Arg/Arg		Gly/Gly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.