Trial Outcomes & Findings for Role of microRNAs in T Cell-Driven Inflammation in Asthma (NCT NCT01484691)

Last Updated: 2022-06-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

55 participants

Primary outcome timeframe

Baseline (cross-sectional analysis)

Results posted on

2022-06-24

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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	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.
Overall Study STARTED	21	22	12
Overall Study COMPLETED	20	19	10
Overall Study NOT COMPLETED	1	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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	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.
Overall Study Withdrawal by Subject	1	1	1
Overall Study Physician Decision	0	2	1

Baseline Characteristics

Role of microRNAs in T Cell-Driven Inflammation in Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Non-asthmatic Controls n=20 Participants 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) n=19 Participants 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	Asthmatics (no Treatment) n=11 Participants 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.	Total n=50 Participants Total of all reporting groups
Region of Enrollment United States	20 participants n=5 Participants	19 participants n=7 Participants	11 participants n=5 Participants	50 participants n=4 Participants
FEV1	3.68 liters STANDARD_DEVIATION 0.93 • n=5 Participants	3.41 liters STANDARD_DEVIATION 1.01 • n=7 Participants	3.52 liters STANDARD_DEVIATION 0.97 • n=5 Participants	3.54 liters STANDARD_DEVIATION 0.99 • n=4 Participants
Age, Continuous	30.05 years STANDARD_DEVIATION 5.34 • n=5 Participants	26.15 years STANDARD_DEVIATION 5.01 • n=7 Participants	32.72 years STANDARD_DEVIATION 13.49 • n=5 Participants	29.16 years STANDARD_DEVIATION 7.63 • n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	5 Participants n=5 Participants	28 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	12 Participants n=7 Participants	8 Participants n=5 Participants	35 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	24 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (cross-sectional analysis)

Population: 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.

Outcome measures

PRIMARY outcome

Timeframe: 8 weeks after randomization to inhaled corticosteroids or no treatment

Population: This analysis population had two groups: 1. Asthmatics who were randomized to treatment with inhaled corticosteroids, 2. Asthmatics who were randomized to 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).

Outcome measures

Adverse Events

Healthy Non-asthmatic Controls

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Asthmatics (Treatment)

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Asthmatics (no Treatment)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Healthy Non-asthmatic Controls n=21 participants at risk 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) n=22 participants at risk 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	Asthmatics (no Treatment) n=12 participants at risk 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.
Injury, poisoning and procedural complications Medication error during bronchoscopy	0.00% 0/21 • 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.	4.5% 1/22 • Number of events 1 • 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.	0.00% 0/12 • 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.

Other adverse events

Other adverse events
Measure	Healthy Non-asthmatic Controls n=21 participants at risk 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) n=22 participants at risk 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	Asthmatics (no Treatment) n=12 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Decreased systolic blood pressure from sedation	0.00% 0/21 • 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.	0.00% 0/22 • 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.	8.3% 1/12 • 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.
Respiratory, thoracic and mediastinal disorders Decreased lung function post-procedure	14.3% 3/21 • 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.	4.5% 1/22 • 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.	8.3% 1/12 • 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.

Additional Information

PI: Prescott G. Woodruff, MD, MPH

University of California, San Francisco

Phone: 415-514-2061

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Healthy Non-asthmatic Controls n=19 Participants 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.	Asthmatics (Baseline) n=25 Participants 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.
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir1	13.2 Normalized log2 copy number Standard Deviation 5.5	10.2 Normalized log2 copy number Standard Deviation 3.0
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir107	13.6 Normalized log2 copy number Standard Deviation 4.5	11.7 Normalized log2 copy number Standard Deviation 3.2
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir128	17.0 Normalized log2 copy number Standard Deviation 5.9	16.5 Normalized log2 copy number Standard Deviation 3.9
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir141	14.6 Normalized log2 copy number Standard Deviation 4.5	13.3 Normalized log2 copy number Standard Deviation 2.0
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir148b	14.5 Normalized log2 copy number Standard Deviation 5.2	11.9 Normalized log2 copy number Standard Deviation 3.3
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir181b	11.5 Normalized log2 copy number Standard Deviation 5.5	10.8 Normalized log2 copy number Standard Deviation 2.6
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir185	12.7 Normalized log2 copy number Standard Deviation 5.0	10.7 Normalized log2 copy number Standard Deviation 2.4
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir194	11.5 Normalized log2 copy number Standard Deviation 8.1	8.7 Normalized log2 copy number Standard Deviation 3.5
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir19a	13.8 Normalized log2 copy number Standard Deviation 7.1	10.4 Normalized log2 copy number Standard Deviation 2.5
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir200a	14.9 Normalized log2 copy number Standard Deviation 7.2	14.9 Normalized log2 copy number Standard Deviation 3.1
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir22	14.2 Normalized log2 copy number Standard Deviation 6.2	12.3 Normalized log2 copy number Standard Deviation 2.9
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir223	12.3 Normalized log2 copy number Standard Deviation 4.6	10.7 Normalized log2 copy number Standard Deviation 1.4
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir23a	14.2 Normalized log2 copy number Standard Deviation 5.0	13.6 Normalized log2 copy number Standard Deviation 2.8
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir26a	10.2 Normalized log2 copy number Standard Deviation 6.7	9.4 Normalized log2 copy number Standard Deviation 2.8
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir320b	13.8 Normalized log2 copy number Standard Deviation 3.4	12.4 Normalized log2 copy number Standard Deviation 2.6
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir598	12.4 Normalized log2 copy number Standard Deviation 2.1	13.4 Normalized log2 copy number Standard Deviation 2.2
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir720	12.1 Normalized log2 copy number Standard Deviation 5.2	11.6 Normalized log2 copy number Standard Deviation 5.1
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir1915	7.7 Normalized log2 copy number Standard Deviation 1.6	8.8 Normalized log2 copy number Standard Deviation 1.1
Difference in Baseline T Cell miRNA Expression Between Asthmatics and Healthy Controls mir1978	11.7 Normalized log2 copy number Standard Deviation 3.7	13.1 Normalized log2 copy number Standard Deviation 2.6

Measure	Healthy Non-asthmatic Controls n=14 Participants 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.	Asthmatics (Baseline) n=7 Participants 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.
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir1	1.5 Normalized log2 copy number Standard Deviation 4.6	-3.0 Normalized log2 copy number Standard Deviation 4.5
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir107	0.86 Normalized log2 copy number Standard Deviation 4.4	-3.7 Normalized log2 copy number Standard Deviation 4.0
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir128	2.0 Normalized log2 copy number Standard Deviation 3.6	-1.6 Normalized log2 copy number Standard Deviation 2.2
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir141	1.2 Normalized log2 copy number Standard Deviation 3.0	1.7 Normalized log2 copy number Standard Deviation 3.7
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir148b	1.5 Normalized log2 copy number Standard Deviation 5.0	-3.1 Normalized log2 copy number Standard Deviation 4.4
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir181b	-0.12 Normalized log2 copy number Standard Deviation 4.9	-1.7 Normalized log2 copy number Standard Deviation 4.3
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir185	0.72 Normalized log2 copy number Standard Deviation 3.8	-2.2 Normalized log2 copy number Standard Deviation 3.4
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir194	-0.73 Normalized log2 copy number Standard Deviation 5.3	-0.37 Normalized log2 copy number Standard Deviation 2.8
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir19a	0.053 Normalized log2 copy number Standard Deviation 3.8	-2.4 Normalized log2 copy number Standard Deviation 3.0
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir200a	-1.4 Normalized log2 copy number Standard Deviation 3.9	-2.2 Normalized log2 copy number Standard Deviation 2.4
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir22	0.059 Normalized log2 copy number Standard Deviation 4.6	-2.7 Normalized log2 copy number Standard Deviation 3.7
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir223	0.90 Normalized log2 copy number Standard Deviation 3.3	-1.0 Normalized log2 copy number Standard Deviation 3.0
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir23a	1.5 Normalized log2 copy number Standard Deviation 3.8	-2.8 Normalized log2 copy number Standard Deviation 1.5
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir26a	1.2 Normalized log2 copy number Standard Deviation 3.6	-0.43 Normalized log2 copy number Standard Deviation 5.4
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir320b	0.86 Normalized log2 copy number Standard Deviation 7.6	1.8 Normalized log2 copy number Standard Deviation 3.7
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir598	-0.20 Normalized log2 copy number Standard Deviation 3.3	-3.5 Normalized log2 copy number Standard Deviation 3.0
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir720	-1.9 Normalized log2 copy number Standard Deviation 6.6	-0.87 Normalized log2 copy number Standard Deviation 4.3
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir1915	-0.49 Normalized log2 copy number Standard Deviation 2.1	0.26 Normalized log2 copy number Standard Deviation 1.7
Change From Baseline of T Cell miRNA Expression at 8 Weeks in Asthmatics in Response to Inhaled Corticosteroids vs. no Treatment mir1978	2.3 Normalized log2 copy number Standard Deviation 5.1	-1.5 Normalized log2 copy number Standard Deviation 2.5