Pharmacogenetics of b2-Agonists in Asthma.

NCT00708227 | Completed Results

• 2 other identifiers: 82211K23HL081245
• Study Type: observational
• Target: 88
• Locations: 1 country
• Sites: 1

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).

Conditions

Asthma

Keywords

Asthma; Pharmacogenetics; Salmeterol; African American; White

Outcome Measures

Primary Outcomes (3)

• Log10 PC20 to Methacholine After Visit 2

  Visit 2 log10 PC20 after receiving 2 weeks of Flovent

  Visit 2:12 hours after last dose of Flovent

• Log10 PC20 to Methacholine After Visit 3

  Visit 3 Log10 PC20 after receiving 2 weeks of Advair

  Visit 3:12 hours after the last dose of Advair

• Log10 PC20 to Methacholine After Visit 4

  Visit 4 log10 PC20 to Methacholine after stopping Advair

  36 hours after the last dose of Advair

Secondary Outcomes (3)

• 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.

• 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

• 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

Study Arms (4)

Whites ADRB2:ARG16ARG

All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.

Whites ADRB2:GLY16GLY

All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.

African American ADRB2:ARG16ARG

All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.

African American ADRB2:GLY16GLY

All participants receive fluticasone for 2-weeks followed by fluticasone / salmeterol for 2-weeks at a dose commensurate with baseline inhaled corticosteroid dose. All participants receive ipratropium bromide for symptom rescue therapy.

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population was Whites and African Americans with specific ADRB2 diplotypes aged 10 years or older with physician diagnosed asthma according to American Thoracic Society criteria for at least 3 months, forced expiratory volume in the first second (FEV1) \>= 60% of predicted normal values for age, height, and gender, and a methacholine challenge test provocative concentration (20% fall in FEV1) of \<=12\]mg/ml.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nemours Children's Clinic: lead
• University of Florida: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Related Publications (1)

• Blake K, Cury JD, Hossain J, Tantisira K, Wang J, Mougey E, Lima J. Methacholine PC20 in African Americans and whites with asthma with homozygous genotypes at ADRB2 codon 16. Pulm Pharmacol Ther. 2013 Jun;26(3):342-7. doi: 10.1016/j.pupt.2013.01.009. Epub 2013 Feb 4.

  PMID: 23384627 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

The purpose of the epigenetic substudy is to collecting blood is for exploratory research into epigenetic effects of salmeterol therapy. Blood was collected at Visit 2 and Visit 3. Steps: * Obtain informed consent * Label vacutainer tube with patient's study ID number, visit number, date of collection (use a sharpee pen) * Collect 10mL blood sample into purple top tube before starting methacholine challenge (must be done before any albuterol is given at the visit) * Immediately place tube in crushed ice or in refrigerator * Spin tube; freeze tube with cells for future genotyping/methylation studies; divide plasma as equally as possible between the 3 cryotubes, freeze the EDTA tube and 3 cryotubes.

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Kathryn Blake
• Organization: Nemours Children's Specialty Care

kathryn.blake@nemours.org

9046973806

Study Officials

• Kathryn Blake, Pharm.D.

  Nemours Children's Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Scientist

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 2, 2008
• Study Start: September 1, 2007
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: February 22, 2018
• Results First Posted: February 22, 2018

Record last verified: 2018-02

Locations

US (1)