AsthmaNCT00708227

Pharmacogenetics of b2-Agonists in Asthma.

An observational study of Asthma, run by Nemours Children's Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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). Read more about this study

Who is it for?: Ages 10 years and older
Conditions the study is for: Asthma
How many people: 88 participants
Where: 1 siteUnited States
Study dates: Sep 2007to Aug 2012
Phase: Observational
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 10 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

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.

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Nemours Children's Clinic
Jacksonville, Florida, 32207

Other trials in United States

About this study

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).

Read the 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.

Conditions: Asthma
Keywords: Asthma, Pharmacogenetics, Salmeterol, African American, White
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00708227
Study group	Role	What they receive
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Log10 PC20 to Methacholine After Visit 2
Visit 2 log10 PC20 after receiving 2 weeks of Flovent
Measured: 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
Measured: 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
Measured: 36 hours after the last dose of Advair

Secondary outcomes (3)

Bronchodilator Response to Methacholine (PC20) After Visit 2
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2007Aug 2012

First posted2 Jul 2008 (estimated)
Study startSep 2007
Primary completionAug 2012
Study completionAug 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 (1)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
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: Observational
Observational model: Case crossover
Time perspective: Prospective
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00708227
Sponsor's protocol ID: 82211
Other IDs: K23HL081245
Status last verified: Feb 2018
First submitted: 27 Jun 2008
Last updated: 22 Feb 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 23384627

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacogenetics of b2-Agonists in Asthma.
ClinicalTrials.gov ID: NCT00708227
Acronym / sponsor ID: 82211
Conditions: Asthma
Keywords: Asthma, Pharmacogenetics, Salmeterol, African American, White
Study type: Observational
Recruitment status: Completed
Enrolment: 88 participants (actual)
Lead sponsor: Nemours Children's ClinicUniversity, hospital or other
Collaborators: University of Florida, National Heart, Lung, and Blood Institute (NHLBI)
Study start: Sep 2007
Primary completion: Aug 2012 (actual)
Study completion: Aug 2012 (actual)
First posted: 2 Jul 2008 (estimated)
Results: Posted 22 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Observational model: Case crossover
Time perspective: Prospective
Number of arms: 4

Arm	Type	Receives
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.

Who may qualify

Ages: 10 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
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.

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Log10 PC20 to Methacholine After Visit 2
Time frame: 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
Time frame: 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
Time frame: 36 hours after the last dose of Advair
Visit 4 log10 PC20 to Methacholine after stopping Advair

3 secondary outcomes

Bronchodilator Response to Methacholine (PC20) After Visit 2
Time frame: 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
Time frame: 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
Time frame: 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

Results and safety

Results posted to the registry on 22 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Whites ADRB2:ARG16ARG	19	18
Whites ADRb2:GLY16GLY	26	21
African Americans ADRB2:ARG16ARG	18	17
African Americans ADRB2:GLY16GlY	25	22

Primary outcome: Log10 PC20 to Methacholine After Visit 2

Time frame: Visit 2:12 hours after last dose of Flovent. Mean (Standard Deviation). Unit: log10 mg/mL

Measure	Whites ADRB2:ARG16ARG n = 18	Whites ADRB2:Gly16Gly n = 25	African Americans ADRB2:ARG16ARG n = 17	African Americans ADRB2:GLY16GLY n = 23
Value	0.54 (0.65)	0.48 (0.71)	0.16 (0.57)	0.53 (0.67)

Whites ADRB2:ARG16ARG vs Whites ADRB2:Gly16Gly vs African Americans ADRB2:ARG16ARG vs African Americans ADRB2:GLY16GLY: p = 0.27, ANOVA

Population analysed: All participants who had a methacholine challenge at Visit 2. All participants had received Flovent for 2 weeks.

Primary outcome: Log10 PC20 to Methacholine After Visit 3

Time frame: Visit 3:12 hours after the last dose of Advair. Mean (Standard Deviation). Unit: log10 mg/mL

Measure	Whites ADRB2:ARG16ARG n = 18	Whites ADRB2:Gly16Gly n = 23	African Americans ADRB2:ARG16ARG n = 17	African Americans ADRB2:GLY16GLY n = 22
Value	0.75 (0.65)	0.78 (0.60)	0.35 (0.63)	0.75 (0.65)

Whites ADRB2:ARG16ARG vs Whites ADRB2:Gly16Gly vs African Americans ADRB2:ARG16ARG vs African Americans ADRB2:GLY16GLY: p = 0.15, ANOVA

Population analysed: All participants who had a methacholine challenge at Visit 3. All participants had received Advair for 2 weeks.

Primary outcome: Log10 PC20 to Methacholine After Visit 4

Time frame: 36 hours after the last dose of Advair. Mean (Standard Deviation). Unit: log10 mg/mL

Measure	Whites ADRB2:ARG16ARG n = 18	Whites ADRB2:Gly16Gly n = 21	African Americans ADRB2:ARG16ARG n = 17	African Americans ADRB2:GLY16GLY n = 22
Value	0.73 (0.61)	0.89 (0.57)	0.36 (0.52)	0.70 (0.66)

Whites ADRB2:ARG16ARG vs Whites ADRB2:Gly16Gly vs African Americans ADRB2:ARG16ARG vs African Americans ADRB2:GLY16GLY: p = 0.06, ANOVA

Population analysed: All participants who had a methacholine challenge at Visit 4. All participants had discontinued Advair for 36 hours.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected during the study period from Visit 1 through Visit 4 (approximately 4 weeks total follow-up).. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Whites ADRB2:ARG16ARG	0 of 19 (0%)	0 of 19 (0%)	0 of 19
Whites ADRB2:GLY16GLY	0 of 26 (0%)	1 of 26 (3.8%)	0 of 26
African American ADRB2:ARG16ARG	0 of 18 (0%)	0 of 18 (0%)	0 of 18
African American ADRB2:GLY16GLY	0 of 25 (0%)	0 of 25 (0%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23384627Blake 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.

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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.

Kathryn Blake, Pharm.D. principal investigator

Nemours Children's Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Asthma, run by Nemours Children's Clinic at 1 site 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 7 inclusion and 6 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 22 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 22 Feb 2018). 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?

Log10 PC20 to Methacholine After Visit 2 (time frame: Visit 2:12 hours after last dose of Flovent). The study lists 3 primary outcomes in all. 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 NCT00708227, which also lists 1 linked publication.

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 22 Feb 2018.