NCT00200967

Brief Summary

The purpose of this trial is to determine whether regularly scheduled use of an inhaled long-acting beta agonist (salmeterol) in the setting of concomitant use of inhaled corticosteroids (beclomethasone hydroflouroalkane (HFA) inhaler) will have a detrimental effect on asthma control in people who bear the B16-Arg/Arg genotype of the beta-2 adrenergic receptor gene, as compared to people with asthma of similar severity who bear the B16-Gly/Gly genotype.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
87

participants targeted

Target at below P25 for phase_3 asthma

Timeline
Completed

Started Dec 2004

Longer than P75 for phase_3 asthma

Geographic Reach
1 country

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2004

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

September 12, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 20, 2005

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2008

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 2, 2009

Completed
Last Updated

January 23, 2018

Status Verified

December 1, 2017

Enrollment Period

3.2 years

First QC Date

September 12, 2005

Results QC Date

March 5, 2009

Last Update Submit

December 26, 2017

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

  • Morning (AM) Peak Expiratory Flow (PEF) Rate

    Change between placebo salmeterol and active salmeterol for AM PEF rate

    Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

Secondary Outcomes (11)

  • Evening (PM) Peak Expiratory Flow (PEF) Rate

    Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

  • Peak Expiratory Flow (PEF) Variability

    Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

  • Asthma Symptoms

    Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

  • Rescue Medication (Ipratropium and Albuterol) Use

    Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

  • Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator

    Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

  • +6 more secondary outcomes

Study Arms (2)

B16 Arg/Arg

EXPERIMENTAL

B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Drug: salmeterolDrug: beclomethasone HFA

B16 Gly/Gly

EXPERIMENTAL

B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Drug: salmeterolDrug: beclomethasone HFA

Interventions

salmeterolDRUG

50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)

Also known as: Serevent
B16 Arg/ArgB16 Gly/Gly
beclomethasone HFADRUG

240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)

Also known as: QVAR
B16 Arg/ArgB16 Gly/Gly

Eligibility Criteria

Age18 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female, ages 18 and older
  • Clinical history consistent with asthma
  • For subjects regularly using inhaled corticosteroids, FEV1 50% of predicted, methacholine PC20 FEV1 16 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs of inhaled albuterol
  • For subjects not regularly using inhaled corticosteroids, FEV1 40% of predicted, methacholine PC20 FEV1 8 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs of inhaled albuterol
  • Genotype eligibility (determined during screening)

You may not qualify if:

  • Smoker (total smoking history must be less than 10 pack years)
  • Significant unstable medical condition other than asthma
  • History of life-threatening asthma requiring treatment with intubation and mechanical ventilation in the past 10 years
  • Pregnant or lactating

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0130, United States

Location

National Jewish Medical & Research Center

Denver, Colorado, 80206, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27103, United States

Location

University of Wisconsin Madison

Madison, Wisconsin, 53792-3244, United States

Location

Related Publications (1)

  • Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, Ameredes BT, Castro M, Craig TJ, Denlinger L, Fahy JV, Jarjour N, Kazani S, Kim S, Kraft M, Lazarus SC, Lemanske RF Jr, Markezich A, Martin RJ, Permaul P, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Walter MJ, Wasserman SI, Israel E; National Heart, Lung and Blood Institute's Asthma Clinical Research Network. Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009 Nov 21;374(9703):1754-64. doi: 10.1016/S0140-6736(09)61492-6.

    PMID: 19932356RESULT

Related Links

MeSH Terms

Conditions

Asthma

Interventions

Salmeterol XinafoateBeclomethasone

Condition Hierarchy (Ancestors)

Bronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesRespiratory HypersensitivityHypersensitivity, ImmediateHypersensitivityImmune System Diseases

Intervention Hierarchy (Ancestors)

AlbuterolEthanolaminesAmino AlcoholsAlcoholsOrganic ChemicalsAminesPhenethylaminesEthylaminesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Chlorinated

Limitations and Caveats

The study used a moderately high dose of ICS. Genotype-specific effects may be evident at lower doses of ICS often used in combination therapy. Also, short-acting β2-agonists have been shown to have genotype-specific effects on asthma outcomes.

Results Point of Contact

Title
Vernon M. Chinchilli
Organization
Penn State College of Medicine
vchinchi@psu.edu
717-531-4262

Study Officials

  • Homer Boushey

    University of California, San Francisco

    PRINCIPAL INVESTIGATOR

  • Mario Castro

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

  • Vernon M. Chinchilli, PhD

    Milton S. Hershey Medical Center

    PRINCIPAL INVESTIGATOR

  • Elliot Israel

    Brigham and Women's Hospital

    PRINCIPAL INVESTIGATOR

  • Robert Lemanske

    University of Wisconsin, Madison

    PRINCIPAL INVESTIGATOR

  • Richard Martin

    National Jewish Medical & Research Center

    PRINCIPAL INVESTIGATOR

  • Stephen Peters

    Wake Forest University Health Sciences

    PRINCIPAL INVESTIGATOR

  • Stephen Wasserman

    University of California, San Diego

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Chair, Department of Public Health Sciences

Study Record Dates

First Submitted

September 12, 2005

First Posted

September 20, 2005

Study Start

December 1, 2004

Primary Completion

February 1, 2008

Study Completion

February 1, 2008

Last Updated

January 23, 2018

Results First Posted

June 2, 2009

Record last verified: 2017-12

Locations

US(7)