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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This will be a single center study of asthmatic subjects and healthy controls which will investigate mechanisms of asthma through detailed molecular analysis of airway tissues and fluids. The primary goal will be investigate the role of microRNAs in Th2-driven inflammation in asthma. The investigators hypothesize that asthma is associated with abnormal expression of miRNAs in T cells which favors differentiation into Th2-cells. The investigators further hypothesize that asthma is heterogeneous based on the presence and absence of Th2-driven inflammation and that abnormalities in T cell miRNA expression will be most prominent in a subgroup with high levels of Th2-driven inflammation (as assessed using molecular markers that the investigators have previously established). Finally, the investigators hypothesize that inhaled corticosteroids will normalize the T-cell miRNA abnormalities observed in asthma, as corticosteroids treat Th2-driven inflammation. The samples collected will also facilitate the pursuit of secondary analyses designed to investigate mechanisms of inflammation and remodeling in asthma as well as molecular phenotypes of asthma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy non-asthmatic controls | No Intervention | Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression. | |
| Asthmatics (treatment) | Active Comparator | Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. |
|
| Asthmatics (no treatment) | No Intervention | Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Budesonide | Drug | Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls | Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011. | Baseline (cross-sectional analysis) |
| Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment | Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05). | 8 weeks after randomization to inhaled corticosteroids or no treatment |
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Group A:
Inclusion Criteria:
Group B:
Inclusion Criteria:
Male and female subjects between the ages of 18 and 70 years
History of asthma
No use of oral or inhaled corticosteroids for the treatment of asthma in the past 6 weeks
Hyperreactivity to methacholine (PC20FEV1 Methacholine ≤ 8.0 mg/mL)
At least one of the following symptoms, beta agonist use, or FEV1 criteria:
Groups A & B:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Prescott G Woodruff, MD, MPH | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco | San Francisco | California | 94143 | United States |
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| Label | URL |
|---|---|
| UCSF Airway Clinical Research Center | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Non-asthmatic Controls | Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression. |
| FG001 | Asthmatics (Treatment) | Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks |
| FG002 | Asthmatics (no Treatment) | Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The sample size for baseline analysis (n=50) does not match the overall enrolled participants (n=55) because the investigators only included samples for baseline analysis if participants completed all visits and had analyzable samples from those visits.
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Non-asthmatic Controls | Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression. |
| BG001 | Asthmatics (Treatment) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls | Identification of T cell miRNAs which are differentially expressed in asthma as compared to healthy controls. The investigators will measure a panel of ~200 miRNAs by qPCR (yielding normalized copy numbers for each miR) and identify differential expressed based on a false discovery rate <0.05. Normalized copy numbers from this qPCR experiment were established using the "global mean-normalization" approach as described in the paper by Barbara D'haene et al. entitled "miRNA expression profiling - from reference genes to global mean normalization" published in MicroRNA Expression profiling Methods and Protocols, Springer Verlag, Feb 2011. | The study enrolled two groups of subjects: 1. Healthy Non-asthmatic Controls, 2. Asthmatics (who were subsequently randomized to inhaled corticosteroids or no treatment). This analysis compares pre-randomization values in group 1 healthy non-asthmatics controls to group 2 asthmatics because the scientific goal is to identify miRNAs differentially expressed in asthma. | Posted | Mean | Standard Deviation | Normalized log2 copy number | Baseline (cross-sectional analysis) |
Participants were monitored for adverse events during their study participation, which ranged from 2 weeks to 10 weeks depending on the group to which they were assigned.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Non-asthmatic Controls | Healthy non-asthmatic controls who will be studied at one point in time and serve as a control group for the baseline bronchoscopy and evaluation of T-cell miRNA expression. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Medication error during bronchoscopy | Injury, poisoning and procedural complications | Non-systematic Assessment | This event was unrelated to study drug. During a bronchoscopy, the participant was erroneously given epinephrine by the procedure nurse. This event was followed to completion and reported to the IRB, OHRP, sponsor, and medical center. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Decreased systolic blood pressure from sedation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| PI: Prescott G. Woodruff, MD, MPH | University of California, San Francisco | 415-514-2061 | prescott.woodruff@ucsf.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D019819 | Budesonide |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks |
| BG002 | Asthmatics (no Treatment) | Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| FEV1 | The volume of air exhaled in the first second of a forced exhalation maneuver, in liters. | Mean | Standard Deviation | liters |
|
| ID | Title | Description |
|---|
| OG000 | Healthy Non-asthmatic Controls | Healthy non-asthmatic controls who underwent bronchoscopy at one time point and served as a control group for the asthmatics group for evaluation of T-cell miRNA expression. |
| OG001 | Asthmatics (Baseline) | All steroid-naïve asthmatics. These subjects were studied before and after randomization to study drug or no treatment. The pre-randomization data were collected on these asthmatics as one uniform group for comparison to healthy controls. These subjects then underwent bronchoscopy and T-cell miRNA measurement at pre-randomization and again 8 weeks after randomization to inhaled corticosteroids or no treatment. |
|
|
|
| Primary | Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment | Identification of T cell miRNAs which were reduced in asthmatics who were randomized to inhaled corticosteroids as compared to those randomized to no treatment. The investigators will measure the same miRNAs by qPCR as identified in the other Primary Outcome and define a significant change using a multiple comparison adjusted p-value (false discovery rate <0.05). | This analysis population had two groups: 1. Asthmatics who were randomized to treatment with inhaled corticosteroids, 2. Asthmatics who were randomized to no treatment. | Posted | Mean | Standard Deviation | Normalized log2 copy number | 8 weeks after randomization to inhaled corticosteroids or no treatment |
|
|
|
|
| 0 |
| 21 |
| 0 |
| 21 |
| 3 |
| 21 |
| EG001 | Asthmatics (Treatment) | Steroid-naïve asthma (randomized to 8 weeks of treatment with inhaled corticosteroids). Asthmatics not on inhaled corticosteroids, randomized to inhaled budesonide, 1 puff (180mcg) twice a day for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline (before corticosteroids) and again after treatment with inhaled corticosteroids. Budesonide: Inhaled powder of inhaled corticosteroid, 1 puff (180mcg) twice a day for 8-10 weeks | 0 | 22 | 1 | 22 | 1 | 22 |
| EG002 | Asthmatics (no Treatment) | Steroid-naïve asthma (randomized to 8 weeks of no inhaled corticosteroid treatment). Asthmatics not on inhaled corticosteroids, randomized to no change in treatment for 8-10 weeks. These subjects will undergo bronchoscopy and T-cell miRNA measurement at baseline and again after 8 weeks without treatment with inhaled corticosteroids. | 0 | 12 | 0 | 12 | 2 | 12 |
|
| Decreased lung function post-procedure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| mir107 |
|
|
| mir128 |
|
|
| mir141 |
|
|
| mir148b |
|
|
| mir181b |
|
|
| mir185 |
|
|
| mir194 |
|
|
| mir19a |
|
|
| mir200a |
|
|
| mir22 |
|
|
| mir223 |
|
|
| mir23a |
|
|
| mir26a |
|
|
| mir320b |
|
|
| mir598 |
|
|
| mir720 |
|
|
| mir1915 |
|
|
| mir1978 |
|
|
mir107
| t-test, 2 sided |
| 0.26 |
This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. |
| Mean Difference (Net) |
| 4.52 |
| 2-Sided |
| Superiority |
| mir128 | t-test, 2 sided | 0.26 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 3.57 | 2-Sided | Superiority |
| mir141 | t-test, 2 sided | 0.87 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | -0.58 | 2-Sided | Superiority |
| mir148b | t-test, 2 sided | 0.29 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 4.57 | 2-Sided | Superiority |
| mir181b | t-test, 2 sided | 0.75 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 1.56 | 2-Sided | Superiority |
| mir185 | t-test, 2 sided | 0.36 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 2.90 | 2-Sided | Superiority |
| mir194 | t-test, 2 sided | 0.89 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | -0.36 | 2-Sided | Superiority |
| mir19a | t-test, 2 sided | 0.48 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 2.48 | 2-Sided | Superiority |
| mir200a | t-test, 2 sided | 0.87 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 0.75 | 2-Sided | Superiority |
| mir22 | t-test, 2 sided | 0.53 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 2.78 | 2-Sided | Superiority |
| mir223 | t-test, 2 sided | 0.57 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 1.91 | 2-Sided | Superiority |
| mir23a | t-test, 2 sided | 0.26 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 4.27 | 2-Sided | Superiority |
| mir26a | t-test, 2 sided | 0.75 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 1.66 | 2-Sided | Superiority |
| mir320b | t-test, 2 sided | 0.89 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | -0.91 | 2-Sided | Superiority |
| mir598 | t-test, 2 sided | 0.26 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 3.32 | 2-Sided | Superiority |
| mir720 | t-test, 2 sided | 0.87 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | -0.99 | 2-Sided | Superiority |
| mir1915 | t-test, 2 sided | 0.74 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | -0.75 | 2-Sided | Superiority |
| mir1978 | t-test, 2 sided | 0.36 | This p value is adjusted for multiple comparisons using the false discovery rate (FDR) approach and a p value <0.05 is taken for significance. | Mean Difference (Net) | 3.77 | 2-Sided | Superiority |