Mild Persistent Asthma
Conditions
Keywords
Leukotriene Antagonists, Bronchodilator response
Brief summary
This study aims to identify markers to prove rapid improvement of lung function, airway inflammation and bronchodilator response after 2-week LTRA administration.
Detailed description
This study is a randomized, double-blind, placebo-controlled, cross-over study with a washout period of at least one week between each study period. After an initial screening visit, subjects entered a screening period of one to two weeks to ensure clinical stability without medication, which means absence of daily asthma symptoms. Eligible subjects were randomized into either the treatment portion of the trial, in which subjects received montelukast (4 mg or 5 mg) or matching placebo monotherapy in a randomized manner. During each treatment period, which lasted 2 weeks, the study medication was administered between 8:00 and 9:00 A.M. Short acting bronchodilator (for severe symptoms) was permitted during the study period but was withheld 24 hours prior to bronchodilator challenge test. Inclusion criteria will be mild persistent asthma children old enough to cooperate on performing pulmonary function testing, children with no respiratory symptoms 4 weeks prior to the beginning of the study. Exclusion criteria will be the following: respiratory symptoms including cough, wheezing, dyspnea, or shortness of breath, presence of acute or chronic upper respiratory infections, anatomical nasal disorders (ex, nasal polyps, septum deviation, etc.), previous or current specific immunotherapy, use of systemic corticosteroids, or admission or visit of the emergency department during the previous 4 weeks.
Interventions
DRUGMontelukast to placebo
Subjects will receive montelukast (4 mg or 5 mg) Each treatment period consists of 2 weeks
Subjects will receive matching placebo. Each treatment period consists of 2 weeks
Sponsors
Merck Sharp & Dohme LLC
CHA University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* children diagnosed with mild persistent asthma patients based on the GINA guidelines * children old enough to cooperate in performing pulmonary function testing * legal guardians who sufficiently listen to the purpose and voluntarily agree with the participation to sign a written consent approved by IRB * children with no respiratory symptoms 4 weeks prior to the beginning of the study * children without chronic respiratory symptoms.
Exclusion criteria
* presence of acute or chronic upper respiratory infections, anatomical nasal disorders (ex, nasal polyps, septum deviation, etc.), previous or current specific immunotherapy. * use of systemic corticosteroids in past 4 weeks. * admission or visit of the emergency department in past 4 weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Lung Function in MMEF | up to 2 weeks | Baseline lung function in maximal mid-expiratory flow before the administration of bronchodilator |
| Baseline Lung Function of Rrs 5 With IOS Before the Bronchodilator (Pre-Rrs5) | up to 2 weeks | Pre Rrs 5: Resistance at 5Hz before the administration of bronchodilator |
| Baseline Lung Function of Xrs5 With IOS Before the Bronchodilator (Pre-Xrs 5) | up to 2 weeks | Pre Xrs 5: Reactance at 5Hz before the administration of bronchodilator |
| Baseline Lung Function of Rrs10 With IOS Before the Bronchodilator | up to 2 weeks | Pre Rrs10: Resistance at 10Hz before the administration of bronchodilator |
| Baseline Lung Function of Xrs10 With IOS Before the Bronchodilator (Pre-Xrs10) | up to 2 weeks | Pre Xrs 10: Reactance at 10Hz before the administration of bronchodilator |
| Baseline Lung Function of FEV1 Before the Bronchodilator | up to 2 weeks | baseline lung function in forced expiratory volume in 1 second before the administration of bronchodilator |
| Baseline Lung Function of FEV1/FVC Before the Bronchodilator | up to 2 weeks | baseline lung function in forced expiratory volume in 1 second/forced vital capacity before the administration of bronchodilator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change (%) of FEV1 After the Bronchodilator | up to 2 weeks | Relative change in percentage of FEV1 after the bronchodilator, 2weeks after placebo and montelukast administration Relative change (%) in FEV1 = (((FEV1 post-bronchodilator)-(FEV1 pre-bronchodilator))/baseline FEV1) x 100 |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subjects All subjects | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Subjects |
|---|---|
| Age, Continuous | 6.41 years STANDARD_DEVIATION 0.88 |
| Lung function (Forced Expiratory Volume 1/Forced Vital Capacity, predicted %) | 86.1 % STANDARD_DEVIATION 2.7 |
| Lung function (Forced Expiratory Volume 1, predicted %) | 92.9 % STANDARD_DEVIATION 4.4 |
| oscillometric lung fuction(Reactance at 5Hz, z-score) | -1.14 z-score STANDARD_DEVIATION 0.55 |
| oscillometric lung function (Resistance at 5Hz, z-score) | 0.36 z-score STANDARD_DEVIATION 0.25 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 7 / 30 | 1 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 | 0 / 32 |
Outcome results
Primary
Baseline Lung Function in MMEF
Baseline lung function in maximal mid-expiratory flow before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function in MMEF | 1.40 L/s | Standard Deviation 0.54 |
| 2 Weeks After Placebo Administration | Baseline Lung Function in MMEF | 1.38 L/s | Standard Deviation 0.59 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function in MMEF | 1.46 L/s | Standard Deviation 0.5 |
Primary
Baseline Lung Function of FEV1 Before the Bronchodilator
baseline lung function in forced expiratory volume in 1 second before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of FEV1 Before the Bronchodilator | 1.28 L/s | Standard Deviation 0.41 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of FEV1 Before the Bronchodilator | 1.25 L/s | Standard Deviation 0.47 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of FEV1 Before the Bronchodilator | 1.28 L/s | Standard Deviation 0.46 |
Primary
Baseline Lung Function of FEV1/FVC Before the Bronchodilator
baseline lung function in forced expiratory volume in 1 second/forced vital capacity before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of FEV1/FVC Before the Bronchodilator | 83.55 none (ratio) | Standard Deviation 16.33 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of FEV1/FVC Before the Bronchodilator | 83.04 none (ratio) | Standard Deviation 1.22 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of FEV1/FVC Before the Bronchodilator | 85.93 none (ratio) | Standard Deviation 8.06 |
Primary
Baseline Lung Function of Rrs10 With IOS Before the Bronchodilator
Pre Rrs10: Resistance at 10Hz before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of Rrs10 With IOS Before the Bronchodilator | 0.57 kPa/L/s | Standard Deviation 0.11 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of Rrs10 With IOS Before the Bronchodilator | 0.55 kPa/L/s | Standard Deviation 0.15 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of Rrs10 With IOS Before the Bronchodilator | 0.55 kPa/L/s | Standard Deviation 0.12 |
Primary
Baseline Lung Function of Rrs 5 With IOS Before the Bronchodilator (Pre-Rrs5)
Pre Rrs 5: Resistance at 5Hz before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of Rrs 5 With IOS Before the Bronchodilator (Pre-Rrs5) | 0.73 kPa/L/s | Standard Deviation 0.15 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of Rrs 5 With IOS Before the Bronchodilator (Pre-Rrs5) | 0.74 kPa/L/s | Standard Deviation 0.2 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of Rrs 5 With IOS Before the Bronchodilator (Pre-Rrs5) | 0.73 kPa/L/s | Standard Deviation 0.15 |
Primary
Baseline Lung Function of Xrs10 With IOS Before the Bronchodilator (Pre-Xrs10)
Pre Xrs 10: Reactance at 10Hz before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of Xrs10 With IOS Before the Bronchodilator (Pre-Xrs10) | -0.15 kPa/L/s | Standard Deviation 0.22 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of Xrs10 With IOS Before the Bronchodilator (Pre-Xrs10) | -0.20 kPa/L/s | Standard Deviation 0.1 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of Xrs10 With IOS Before the Bronchodilator (Pre-Xrs10) | -0.19 kPa/L/s | Standard Deviation 0.07 |
Primary
Baseline Lung Function of Xrs5 With IOS Before the Bronchodilator (Pre-Xrs 5)
Pre Xrs 5: Reactance at 5Hz before the administration of bronchodilator
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Baseline Lung Function of Xrs5 With IOS Before the Bronchodilator (Pre-Xrs 5) | -0.34 kPa/L/s | Standard Deviation 0.11 |
| 2 Weeks After Placebo Administration | Baseline Lung Function of Xrs5 With IOS Before the Bronchodilator (Pre-Xrs 5) | -0.36 kPa/L/s | Standard Deviation 0.15 |
| 2 Weeks After Montelukast Administration | Baseline Lung Function of Xrs5 With IOS Before the Bronchodilator (Pre-Xrs 5) | -0.34 kPa/L/s | Standard Deviation 0.1 |
Secondary
Relative Change (%) of FEV1 After the Bronchodilator
Relative change in percentage of FEV1 after the bronchodilator, 2weeks after placebo and montelukast administration Relative change (%) in FEV1 = (((FEV1 post-bronchodilator)-(FEV1 pre-bronchodilator))/baseline FEV1) x 100
Time frame: up to 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline Lung Function | Relative Change (%) of FEV1 After the Bronchodilator | 9.68 % (relative change) | Standard Deviation 13.31 |
| 2 Weeks After Placebo Administration | Relative Change (%) of FEV1 After the Bronchodilator | 5.65 % (relative change) | Standard Deviation 10.34 |