Pharmacogenetics of b2-Agonists in Asthma.

Completed

• Conditions: Asthma

• Registration Number: NCT00708227
• Lead Sponsor: Nemours Children's Clinic

Brief Summary

This study will help to find out if having a certain genetic makeup influences how a person with asthma responds to salmeterol, one of the two drugs in Advair(R).

Detailed Description

Patients are being asked to take part in this research study because they have asthma. This clinical research study is being done to see if an asthmatic's gene make-up (DNA is made up of genes) affects the way they respond to a particular asthma medication called salmeterol. Certain genes make people tall or short. Certain genes give people brown or black hair. Similarly, certain genes may be associated with the way patients respond to asthma medications.

Salmeterol xinafoate (a long acting bronchodilator) and fluticasone propionate (an inhaled corticosteroid) are the medicines contained in Advair Diskus. During this study, patients with asthma will receive fluticasone inhaler (called Flovent) and Advair Diskus. The investigators want to find out if patients with asthma with certain genes respond in different ways to the salmeterol in Advair Diskus. The investigators also want to find out if patients with asthma with certain genes who are treated with salmeterol for two weeks have their airways open up less than usual when they use albuterol.

Study Timeline

• Study Start: 2007-09
• Study First Submitted: 2008-06-27
• Study First Submitted QC: 2008-07-01
• Study First Posted: 2008-07-02
• Primary Completion: 2012-08
• Study Completion: 2012-08
• Results First Submitted: 2017-12-20
• Status Verified: 2018-02
• Results First Submitted QC: 2018-02-20
• Last Update Submitted: 2018-02-20
• Results First Posted: 2018-02-22
• Last Update Posted: 2018-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

• Diplotype: Whites with specific diplotype and African Americans with specific diplotypes.
• Gender: Male or female. Women are eligible if they are not pregnant or lactating. Females subjects of childbearing potential will undergo a urine pregnancy test prior to each methacholine challenge test.
• Age: 10 years and older.
• Asthma Diagnosis: Physician diagnosed asthma according to American Thoracic Society criteria for at least 3 months.
• Asthma Therapy: There is no requirement for previous asthma therapy to be included in this study.
• Asthma Severity: forced expiratory volume in the first second (FEV1) must be >= 60% of predicted normal values for age, height, and gender.
• methacholine challenge test provocative concentration (20% fall in FEV1) of <=12]mg/ml.

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Exclusion Criteria

• History of life-threatening asthma: Any episode of asthma requiring intubation associated with hypercapnia, respiratory arrest, or hypoxic seizures.
• Asthma instability: Hospitalization for asthma within 3 months of Visit 1.
• Concurrent respiratory disease: Any respiratory disease other than asthma.
• Sensitivities: Sensitivities to methacholine, Flovent® MDI, ipratropium bromide, albuterol, or Advair Diskus® that would put the safety of the subject at risk.
• Respiratory Tract Infection: Any sinus, middle ear, oropharyngeal, upper or lower respiratory tract infection that has not resolved at least 2 weeks immediately preceding Visit 1, or for which antibiotic therapy has not been completed at least 2 weeks prior to Visit 1.
• Expected exposure to pollen allergen to which the patient is sensitive (by medical history of symptoms) during the 29 day study period. These patients can be studied when pollen exposure to which they are sensitive will not occur.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Log10 PC20 to Methacholine After Visit 2	Visit 2:12 hours after last dose of Flovent	Visit 2 log10 PC20 after receiving 2 weeks of Flovent
Log10 PC20 to Methacholine After Visit 3	Visit 3:12 hours after the last dose of Advair	Visit 3 Log10 PC20 after receiving 2 weeks of Advair
Log10 PC20 to Methacholine After Visit 4	36 hours after the last dose of Advair	Visit 4 log10 PC20 to Methacholine after stopping Advair

Secondary Outcome Measures

Name	Time	Method
Bronchodilator Response Following Methacholine Challenge at Visit 4	0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 36 hours after the last dose of Advair	The area under the curve (AUC) bronchodilator response after Visit 4 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had discontinued Advair for 36 hours.
Bronchodilator Response to Methacholine (PC20) After Visit 2	0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 12 hours after the last dose of Flovent.	The area under the curve (AUC) bronchodilator response after Visit 2 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had received Flovent for 2 weeks at Visit 2.
Bronchodilator Response Following Methacholine Challenge at Visit 3	0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes after nebulization was complete which occurred 12 hours after the last dose of Advair	The area under the curve (AUC) bronchodilator response after Visit 3 methacholine challenge. 2.5mg of albuterol was administered at the time of maximal brochoconstriction once the methacholine PC20 was reached and the change in FEV1 was measured over the next 60 minutes post albuterol administration (bronchodilator response). FEV1 was measured at the following times: 0 (immediately upon completion of nebulization) and at 1, 3, 5, 10, 15, 20, 30, 45, and 60 minutes. Participants had received Advair for 2 weeks at Visit 3.

Trial Locations

Locations (1)

Nemours Children's Clinic; 🇺🇸 Jacksonville, Florida, United States