Trial Outcomes & Findings for Study of the Mechanisms of Asthma (NCT NCT00595153)

Last Updated: 2014-01-20

Results Overview

The primary outcome measure for this study is the scaled mean value of three gene expression markers of IL-13 in the airway: PERIOSTIN, calcium-activated chloride channel regulator 1 (CLCA1), and plasminogen activator inhibitor-2 (SERPINB2). First, for each of the three interleukin-13 (IL-13) signature genes, the log (base-2) transformed relative expression value for each subject is measured using real-time polymerase chair reaction (PCR) and normalized with the geometric mean of 5 housekeeping genes. Next, these values are centered (by subtracting the mean for that gene) and scaled (by dividing by the standard deviation for that gene) so that each gene makes an equal, assay-independent contribution to the Th2 phenotype. Then, for each subject, the arithmetic mean of the three centered \& scaled genes is calculated, producing the "three-gene-mean" metric.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

127 participants

Primary outcome timeframe

Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks)

Results posted on

2014-01-20

Participant Flow

The MAST study enrolled 103 adults with asthma and 24 healthy controls between 8/2007 to 6/2011. Participants were seen in a clinical research center.

Steroid naïve asthmatics had bronchoscopy before and after an 8 week treatment with inhaled corticosteroids, and asthmatics already taking an inhaled corticosteroid had their treatment standardized for 8 weeks followed by a bronchoscopy. Healthy control subjects participated in a cross-sectional study for characterization and bronchoscopy.

Participant milestones

Participant milestones
Measure	Healthy Control Healthy, non-asthmatics who will not be put on any intervention	Steroid Naive Asthmatics Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Asthmatics on ICS Treatment Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Overall Study STARTED	24	42	61
Overall Study COMPLETED	20	26	36
Overall Study NOT COMPLETED	4	16	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of the Mechanisms of Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Control n=24 Participants Healthy, non-asthmatics who will not be put on any intervention	Steroid Naive Asthmatics n=42 Participants Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Asthmatics on ICS Treatment n=61 Participants Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Total n=127 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants	42 Participants n=7 Participants	61 Participants n=5 Participants	127 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	34.5 years STANDARD_DEVIATION 9.0 • n=5 Participants	32.0 years STANDARD_DEVIATION 11.6 • n=7 Participants	39.0 years STANDARD_DEVIATION 11.9 • n=5 Participants	35.9 years STANDARD_DEVIATION 11.7 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	27 Participants n=7 Participants	34 Participants n=5 Participants	71 Participants n=4 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants	56 Participants n=4 Participants
Region of Enrollment United States	24 participants n=5 Participants	42 participants n=7 Participants	61 participants n=5 Participants	127 participants n=4 Participants

PRIMARY outcome

Timeframe: Healthy Control: Visit 2 (at 1 week); Steroid Naive Asthmatics: Visit 2 (at 1 week); Steroid Treated Asthmatics: Visit 5 (at 9 weeks)

Population: Participants who met inclusion/exclusion requirements and completed all study activities were included in the analysis. Specifically, this included: 1\. Having a bronchoscopy with complete PCR on RNA from epithelial brush samples.

Outcome measures

Outcome measures
Measure	Healthy Control n=19 Participants Healthy, non-asthmatics who will not be put on any intervention	Steroid Naive Asthmatics n=24 Participants Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Asthmatics on ICS Treatment n=21 Participants Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Gene Expression in Airway Secretions and Tissues	-0.66 Relative gene expression level Standard Deviation 0.36	0.54 Relative gene expression level Standard Deviation 0.87	-0.30 Relative gene expression level Standard Deviation 0.60

Adverse Events

Healthy Control

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Steroid Naive Asthmatics

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Asthmatics on ICS Treatment

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Control n=24 participants at risk Healthy, non-asthmatics who will not be put on any intervention	Steroid Naive Asthmatics n=42 participants at risk Asthmatics not on inhaled corticosteroids who will be put on an inhaled steroid during the study Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks	Asthmatics on ICS Treatment n=61 participants at risk Asthmatics, who are already on inhaled corticosteroids who will be put on standardized dose of inhaled corticosteroids Pulmicort : inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks
Respiratory, thoracic and mediastinal disorders Increased asthma symptoms following medication hold	— 0/0	0.00% 0/42	8.2% 5/61 • Number of events 60
Respiratory, thoracic and mediastinal disorders Did not tolerate switch of asthma controller medication	— 0/0	0.00% 0/42	8.2% 5/61 • Number of events 60
Respiratory, thoracic and mediastinal disorders Respiratory symptoms/decreased lung function following bronchoscopy	25.0% 6/24 • Number of events 28	11.9% 5/42 • Number of events 84	8.2% 5/61 • Number of events 60

Additional Information

John V. Fahy, MD, MSc

University of California, San Francisco

Phone: 4154769940

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place