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The Effects of Montelukast on Smokers With Asthma

Sponsor
Inje University (Other)
Overall Status
Completed
CT.gov ID
NCT00712335
Collaborator
(none)
105
Enrollment
1
Location
5
Arms
50.9
Duration (Months)
2.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is:

  1. To compare neutrophilia, eosinophilic inflammatory markers and asthma symptom indices between smokers and non-smokers.

  2. To elucidate the mechanism by which cigarette smokers are resistant to corticosteroids.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Many smokers have insufficient control of their symptoms due to inefficacy of ICS in this subpopulation of asthmatics. Cigarette smoking has been shown to stimulate production of cysLTs. CysLTs could activate production of IL-8 for neutrophilia as well as cause eosinophilia in the airway of asthmatics.

LTRAs are felt to be less efficacious than ICS in smokers with asthma. However, LTRA's unique mechanism of action could be particularly efficacious in preventing worsening symptoms and lung function for smokers with asthma. Given this, along with the fact that ICS are less effective in smokers, targeting cysLT could lead to significant clinical benefits for asthmatic smokers.

Data from this study may possibly serve as crucial data for the significant clinical benefits for asthmatic smokers and determination of the mechanism of corticosteroid resistance in smokers with asthma.

Study Design

Study Type:
Interventional
Actual Enrollment :
105 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Diagnostic
Official Title:
The Effects of Montelukast on Sputum Cells and Inflammatory Markers in Smokers With Asthma
Study Start Date :
Feb 1, 2007
Actual Primary Completion Date :
May 1, 2011
Actual Study Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months

Drug: Fluticasone Propionate
DPI 250 mcg BID for 3 weeks
Other Names:
  • inhaled corticosteroid

    • Drug: Salmeterol
    DPI 50mg BID for 3 weeks
    Other Names:
  • long-acting beta-agonist

    		•
    Experimental: 2

    Asthmatic smoker treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months

    Drug: Montelukast
    PO 10 mg QHS for 3 weeks
    Other Names:
  • leukotriene receptor antagonist

    		•
    Active Comparator: 3

    Non-smoking asthmatics treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months

    Drug: Fluticasone Propionate
    DPI 250 mcg BID for 3 weeks
    Other Names:
  • inhaled corticosteroid

    • Drug: Salmeterol
    DPI 50mg BID for 3 weeks
    Other Names:
  • long-acting beta-agonist

    		•
    Active Comparator: 4

    Non-smoking asthmatic treated with Montelukast only: Montelukast dosage: PO 10 mg QHS for 3 months

    Drug: Montelukast
    PO 10 mg QHS for 3 weeks
    Other Names:
  • leukotriene receptor antagonist

    		•
    No Intervention: 5

    Normal controls

    Outcome Measures

    Primary Outcome Measures

    1. Sputum Neutrophil Percentages [24 weeks]

      Week 24 sputum neutrophil percentages were measured in active treatment groups.

    Secondary Outcome Measures

    1. Sputum Eosinophil Percentages [24 weeks]

      Secondary endpoints of inflammatory markers (sputum eosinophil percentages at 24 weeks) were measured in active treatment groups

    2. Sputum IL-8 Levels [24 weeks]

      Week 24 sputum IL-8 levels in active treatment groups

    3. Sputum GM-CSF Levels [24 weeks]

      Week 24 sputum GM-CSF levels in active treatment groups were measured.

    4. Sputum IFN-gamma/IL-5 Ratios [24 weeks]

      Week 24 sputum IFN-gamma/IL-5 ratios were determined in active treatment groups.

    5. Sputum Eotaxin Levels [24 weeks]

      Week 24 sputum eotaxin levels in active treatment groups were measured.

    6. Sputum RANTES Levels [24 weeks]

      Week 24 sputum RANTES levels in active treatment groups were measured.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    Asthmatics:

    • clinical history of asthma for at least 1 year

    • with evidence of reversible airway obstruction,

    • two documented FEV1 between 60-85%,

    • PC20 < 4mg/ml by methacholine challenge test

    • and average baseline β-agonist use of 2 puffs/day

    Smokers:

    • smoke 1/2 to 2 packs a day

    • with a smoking history of 5-30 pack years

    Non-smokers:
    • Non-smokers will have either never smoked or have stopped smoking cigarettes over 5 years ago
    Exclusion Criteria:

    • positive HCG (for females)

    • have a respiratory tract infection or need oral corticosteroids within the preceding 6 weeks

    • history of COPD or respiratory disorder other than asthma

    • history of psychiatric illness

    • allergy to fluticasone propionate, salmeterol, montelukast or any of their components

    • significant, unstable medical condition other than asthma

    • history of life-threatening asthma exacerbation requiring intubation and mechanical ventilation in the last ten years

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Asthma and Allergy Center, Inje University Sanggye Paik Hospital Seoul Korea, Republic of 139-707

    Sponsors and Collaborators

    • Inje University

    Investigators

    • Principal Investigator: Chang-Keun Kim, MD, PhD, Asthma and Allergy Center, Inje University Sanggye Paik Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Chang-Keun Kim, Dr., Director, Asthma and Allergy Center; Chairman of Pediatrics; Professor of Pediatrics, Inje University
    ClinicalTrials.gov Identifier:
    NCT00712335
    Other Study ID Numbers:
    • MASK2008
    First Posted:
    Jul 9, 2008
    Last Update Posted:
    May 16, 2012
    Last Verified:
    Apr 1, 2012
    Keywords provided by Chang-Keun Kim, Dr., Director, Asthma and Allergy Center; Chairman of Pediatrics; Professor of Pediatrics, Inje University
    asthmatics
    smokers
    inhaled corticosteroids
    leukotriene receptor antagonists
    Additional relevant MeSH terms:
    Asthma
    Fluticasone
    Xhance
    Salmeterol Xinafoate
    Montelukast
    Leukotriene Antagonists

    Study Results

    Participant Flow

    Recruitment Details Recruitment period: January 2008-April 2011 Recruitment location: Asthma and Allergy Center, Inje University Sanggye Paik Hospital
    Pre-assignment Detail After randomization, a 10-day washout period followed in which subjects were taken off all medications except albuterol metered dose inhaler as needed. After the washout period, baseline induced sputum was obtained in each group along with primary and secondary endpoints. This was followed by a 3-week run in period.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Period Title: Overall Study
    STARTED 8 32 11 24 30
    COMPLETED 5 15 6 19 30
    NOT COMPLETED 3 17 5 5 0

    Baseline Characteristics

    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls Total
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment. Total of all reporting groups
    Overall Participants 8 32 11 24 30 105
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    100%
    32
    100%
    11
    100%
    24
    100%
    30
    100%
    105
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.38
    (11.41)
    36.03
    (8.52)
    45.64
    (17.46)
    39.00
    (14.79)
    40.55
    (11.35)
    40.09
    (4.24)
    Sex: Female, Male (Count of Participants)
    Female
    3
    37.5%
    5
    15.6%
    4
    36.4%
    22
    91.7%
    22
    73.3%
    56
    53.3%
    Male
    5
    62.5%
    27
    84.4%
    7
    63.6%
    2
    8.3%
    8
    26.7%
    49
    46.7%
    Region of Enrollment (participants) [Number]
    Korea, Republic of
    8
    100%
    32
    100%
    11
    100%
    24
    100%
    30
    100%
    105
    100%

    Outcome Measures

    1. Secondary Outcome
    Title Sputum Eosinophil Percentages
    Description Secondary endpoints of inflammatory markers (sputum eosinophil percentages at 24 weeks) were measured in active treatment groups
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    We will use ITT and PP protocols for analysis
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [percentage of eosinophils]
    2.33
    (3.01)
    3.60
    (6.43)
    1.60
    (1.34)
    3.26
    (6.10)
    2. Primary Outcome
    Title Sputum Neutrophil Percentages
    Description Week 24 sputum neutrophil percentages were measured in active treatment groups.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    We will be using intention-to-treat and per protocol for analysis.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [percentage of neutrophils]
    86.00
    (8.22)
    72.53
    (24.14)
    89.33
    (6.41)
    79.84
    (17.07)
    3. Secondary Outcome
    Title Sputum IL-8 Levels
    Description Week 24 sputum IL-8 levels in active treatment groups
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    We will ITT and PP protocols for analysis
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [pg/ml]
    334545
    (804,831)
    26,300
    (74,106)
    3602
    (2342)
    317778
    (738415)
    4. Secondary Outcome
    Title Sputum GM-CSF Levels
    Description Week 24 sputum GM-CSF levels in active treatment groups were measured.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    We will use ITT and PP for analysis
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [pg/ml]
    17.60
    (24.67)
    15.18
    (16.37)
    13.92
    (10.66)
    12.16
    (18.05)
    5. Secondary Outcome
    Title Sputum IFN-gamma/IL-5 Ratios
    Description Week 24 sputum IFN-gamma/IL-5 ratios were determined in active treatment groups.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT and PP were used for analysis.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [ratio]
    627.4
    (742.1)
    272.4
    (387.1)
    183.8
    (82.70)
    279.0
    (563.3)
    6. Secondary Outcome
    Title Sputum Eotaxin Levels
    Description Week 24 sputum eotaxin levels in active treatment groups were measured.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT and PP were used for analysis.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [pg/ml]
    47.13
    (41.93)
    87.90
    (93.15)
    65.14
    (25.54)
    64.61
    (44.07)
    7. Secondary Outcome
    Title Sputum RANTES Levels
    Description Week 24 sputum RANTES levels in active treatment groups were measured.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    ITT and PP were used for analysis.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    Measure Participants 5 15 6 19 0
    Mean (Standard Deviation) [pg/ml]
    42.79
    (32.47)
    44.03
    (40.41)
    41.78
    (19.93)
    36.41
    (29.93)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description Normal Controls were not assessed for Adverse Events because they were not administered any treatment.
    Arm/Group Title Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Arm/Group Description Asthmatic smokers treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Asthmatic smoker treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Non-smoking asthmatic treated with combination therapy: Fluticasone propionate dosage - DPI 250 mcg BID for 3 months Salmeterol dosage - DPI 50 mcg BID for 3 months Non-smoking asthmatic treated with Montelukast only: Montelukast dosage - PO 10 mg QHS for 3 months Normal controls did not receive any treatment.
    All Cause Mortality
    Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/32 (0%) 0/11 (0%) 0/24 (0%) 0/0 (NaN)
    Other (Not Including Serious) Adverse Events
    Asthmatic Smokers Treated With Combination Therapy Asthmatic Smoker Treated With Montelukast Only Non-smoking Asthmatic Treated With Combination Therapy Non-smoking Asthmatic Treated With Montelukast Only Normal Controls
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/32 (0%) 0/11 (0%) 0/24 (0%) 0/0 (NaN)

    Limitations/Caveats

    It is difficult attaining representative gender ratios (i.e., representative of the general population) when conducting a smoking study in Korea, as smoking by females is still considered culturally taboo.

    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.

    Results Point of Contact

    Name/Title Dr. Chang-Keun Kim
    Organization Inje University
    Phone 82-2-950-8832
    Email kimck@paik.ac.kr
    Responsible Party:
    Chang-Keun Kim, Dr., Director, Asthma and Allergy Center; Chairman of Pediatrics; Professor of Pediatrics, Inje University
    ClinicalTrials.gov Identifier:
    NCT00712335
    Other Study ID Numbers:
    • MASK2008
    First Posted:
    Jul 9, 2008
    Last Update Posted:
    May 16, 2012
    Last Verified:
    Apr 1, 2012