AsthmaPhase 2ACENCT02230189

Study of the Inflammation and Airway Changes That Occur After Exposure to Allergen in Asthmatics

A Phase 2 study testing Segmental airway allergen challenge, Bronchoscopy and Methacholine challenge test in people with Asthma, run by Prescott Woodruff at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Asthma
What is being tested?: Segmental airway allergen challenge, Bronchoscopy and Methacholine challenge test
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 28 participants
Where: 1 siteUnited States
Study dates: Mar 2015to Jan 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Positive skin test to dust mite or cat allergen
Non-Allergic/Non-Asthmatic subjects
Negative skin test to panel of 12 allergens, including dust mite and cat allergen
All groups

Who cannot join

History of intubation for asthma exacerbation
Use of Xolair (omalizumab) within the last 6 months
Immunotherapy with cat or dust mite extract now or in the past 5 years
≥ 10 pack-years smoking or any smoking in the past year
Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection
History of dermatographia

Show all 9Show fewer

History of anaphylaxis to cat allergen
Participation in another research study involving a drug or biologic during the past 30 days
Presence of past or current medical problems/other factors that may pose additional risks from participation or influence study results, as determined per study investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

University of California, San Francisco
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.

This protocol describes a single site mechanistic study to investigate microRNAs (miRNAs) that are differentially expressed in the airway epithelium of patients with asthma at baseline and in response to allergen challenge. We hypothesize that allergen exposure enhances airway smooth muscle contractility and epithelial cell mRNA/miRNA production as a consequence of locally increased T-cell derived cytokine production. The study will involve three visits over the course of approximately 14 days. At Visit 1, participants will be characterized in detail with lung function testing, methacholine challenge testing, and allergen skin prick testing. At Visit 2, participants will undergo bronchoscopy with segmental allergen administration of either cat or dust mite standardized allergen extract. At Visit 3 (either 24 hours later or 7 days later), bronchoscopy will be performed to collect airway samples including bronchoalveolar lavage (BAL), epithelial brushings and endobronchial biopsies. Sample analysis will include measurement of miRNA and mRNA expression in epithelial brushings (RNAseq and qPCR); analysis of cell surface markers on BAL cells and blood cells; and collection of endobronchial biopsies for immunostaining of immune cells localization, immunoblotting of smooth cell protein phosphorylation, analysis of mucin content and smooth muscle cell subculture. A total of 38 subjects (26 asthmatics with stable or well-controlled asthma, 6 allergic non-asthmatics and 6 non-allergic non-asthmatics) will complete the study.

Conditions: Asthma
Being tested: Segmental airway allergen challenge, Bronchoscopy, Methacholine challenge test, Spirometry, Allergen skin prick test
Keywords: Asthma, Allergen challenge
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Segmental airway allergen challengeBiological
BronchoscopyProcedure or surgery
Methacholine challenge testDiagnostic test
SpirometryDiagnostic test
Allergen skin prick testDiagnostic test

Study groups in NCT02230189
Study group	Role	What they receive
Allergen challenge subjects	Experimental	Intervention: Segmental airway allergen challenge Three types of subjects are studied in this arm: 1) Volunteers with neither asthma nor allergy (as established by skin prick testing); 2) Volunteers with allergy (as established by skin prick testing) but without asthma; and 3) Volunteers with both asthma and allergy (as established by skin prick testing) Receives: Biological: Segmental airway allergen challenge; Procedure: Bronchoscopy; Diagnostic Test: Methacholine challenge test; Diagnostic Test: Spirometry; Diagnostic Test: Allergen skin prick test

What is being measured

The primary outcome is the main question the study is designed to answer.

Difference in Expression of Epithelial miRNAs (in Read Counts) 24 Hours After Allergen-challenge as Compared to 24 Hours After Diluent Challenge in Participants With Allergic Asthma
For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 24 hours later. After processing brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(<0.05). The direction of change does not have clinical significance; this was a mechanistic study.
Measured: 24 hours
Difference in Expression of Epithelial miRNAs (in Read Counts) 7 Days After Allergen-challenge as Compared to 7 Days After Diluent Challenge
For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 7 days later. After processing the brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(<0.05). The direction of change does not have clinical significance; this was a mechanistic study.
Measured: 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2015Jan 2020

First posted3 Sep 2014 (estimated)
Study startMar 2015
Primary completionJan 2020
Study completionJan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for AsthmaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Model description: Single group before and after administration of allergen
Masking: None (open label)
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02230189
Sponsor's protocol ID: 14-14224
Other IDs: 5U19AI077439
Acronym: ACE
Status last verified: Jul 2022
First submitted: 28 Aug 2014
Last updated: 16 Aug 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma

All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Mechanistic Study of Epithelial miRNAs and T-cell Recruitment Dynamics That Occur After Allergen Challenge in Patients With Asthma.
ClinicalTrials.gov ID: NCT02230189
Acronym / sponsor ID: ACE / 14-14224
Conditions: Asthma
Keywords: Asthma, Allergen challenge
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Prescott WoodruffUniversity, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: Mar 2015 (actual)
Primary completion: Jan 2020 (actual)
Study completion: Jan 2020 (actual)
First posted: 3 Sep 2014 (estimated)
Results: Posted 16 Aug 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Single group before and after administration of allergen

Arm	Type	Receives
Allergen challenge subjects	Experimental	Biological: Segmental airway allergen challenge, Procedure: Bronchoscopy, Diagnostic Test: Methacholine challenge test, Diagnostic Test: Spirometry, Diagnostic Test: Allergen skin prick testIntervention: Segmental airway allergen challenge Three types of subjects are studied in this arm: 1) Volunteers with neither asthma nor allergy (as established by skin prick testing); 2) Volunteers with allergy (as established by skin prick testing) but without asthma; and 3) Volunteers with both asthma and allergy (as established by skin prick testing)

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Positive skin test to dust mite or cat allergen
Non-Allergic/Non-Asthmatic subjects
Negative skin test to panel of 12 allergens, including dust mite and cat allergen
All groups

Key exclusion criteria (9 listed)

History of intubation for asthma exacerbation
Use of Xolair (omalizumab) within the last 6 months
Immunotherapy with cat or dust mite extract now or in the past 5 years
≥ 10 pack-years smoking or any smoking in the past year
Other lung diseases, such as sarcoidosis, bronchiectasis or active lung infection

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Segmental airway allergen challenge	Biological	Allergen challenge subjects
Bronchoscopy	Procedure or surgery	Allergen challenge subjects
Methacholine challenge test	Diagnostic test	Allergen challenge subjects
Spirometry	Diagnostic test	Allergen challenge subjects
Allergen skin prick test	Diagnostic test	Allergen challenge subjects

Primary outcome

Difference in Expression of Epithelial miRNAs (in Read Counts) 24 Hours After Allergen-challenge as Compared to 24 Hours After Diluent Challenge in Participants With Allergic Asthma
Time frame: 24 hours
For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 24 hours later. After processing brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(<0.05). The direction of change does not have clinical significance; this was a mechanistic study.
Difference in Expression of Epithelial miRNAs (in Read Counts) 7 Days After Allergen-challenge as Compared to 7 Days After Diluent Challenge
Time frame: 7 days
For each participant with Allergic Asthma, a baseline airway epithelial brushing was performed, allergen was instilled into one segment of the lung, and diluent (control) was instilled into another segment. Both segments were brushed for epithelial cells 7 days later. After processing the brushes to RNA and generating RNA sequencing data, the RNA transcript read counts for each gene underwent variance stabilized log normalization. Then we built a regression model which estimated the difference in miRNA read count in the allergen challenged as compared to the baseline sample and the difference in miRNA read count in the diluent challenged segment as compared to baseline for each participant. The change from baseline read count for each miRNA in the allergen samples was compared to the change in the diluent samples and statistical significance was assessed using the unadjusted p-value(<0.05). The direction of change does not have clinical significance; this was a mechanistic study.

Results and safety

Results posted to the registry on 16 Aug 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Allergic Asthmatics(AA)	22	17
Allergic Non-Asthmatics(ANA)	2	2
Non-Allergic Non-Asthmatics(NANA)	4	3

Primary outcome: Difference in Expression of Epithelial miRNAs (in Read Counts) 24 Hours After Allergen-challenge as Compared to 24 Hours After Diluent Challenge in Participants With Allergic Asthma

Time frame: 24 hours. Mean (Standard Deviation). Unit: Normalized log2 copy number

Measure	Allergen Challenge Subjects n = 12	Diluent Challenge Subjects n = 12
miR4521	7.33 (0.79)	6.74 (0.43)
miR107	9.63 (0.61)	9.01 (0.98)
miR891a	7.02 (0.64)	6.56 (0.46)
miR363	9.55 (1.16)	8.77 (1.07)
miR1248	7.02 (0.31)	7.21 (0.48)
miR944	7.12 (0.19)	7.27 (0.36)
miR6806	6.63 (0.22)	6.35 (0.13)
miR103a	12.05 (0.38)	11.7 (0.48)

Allergen Challenge Subjects vs Diluent Challenge Subjects: Mean Difference (Net): 2.11, p = 0.010, t-test, 2 sided
Allergen Challenge Subjects vs Diluent Challenge Subjects: Mean Difference (Net): 0.56, p = 0.010, t-test, 2 sided
Allergen Challenge Subjects vs Diluent Challenge Subjects: Mean Difference (Net): 2.57, p = 0.018, t-test, 2 sided

Population analysed: Our pre-specified primary outcome was limited to Allergic Asthmatics only. The rationale for this is that participants without allergy or asthma do not respond to Allergen Challenge and therefore the changes in miRNA are uninformative.

Primary outcome: Difference in Expression of Epithelial miRNAs (in Read Counts) 7 Days After Allergen-challenge as Compared to 7 Days After Diluent Challenge

Time frame: 7 days. Mean (Standard Deviation). Unit: Normalized log2 copy number

Measure	Allergen Challenge Segment n = 4	Diluent Challenge Segment n = 4
miR6510	7.74 (0.57)	9.2 (0.81)
miR3605	5.92 (0.61)	6.9 (0.8)
miR3912	5.03 (0.53)	5.83 (0.61)
miR15b	6.76 (0.33)	6.09 (0.39)
miR127	7.06 (0.8)	8.54 (1.73)
miR146a	14.14 (1.19)	12.73 (0.8)
miR449b	9.99 (0.54)	8.84 (0.88)
miR21-5p	18.02 (0.33)	17 (0.82)

Allergen Challenge Segment vs Diluent Challenge Segment: Mean Difference (Net): -1.83, p = 0.0, t-test, 2 sided
Allergen Challenge Segment vs Diluent Challenge Segment: Mean Difference (Net): -2.09, p = 0, t-test, 2 sided
Allergen Challenge Segment vs Diluent Challenge Segment: Mean Difference (Net): -5.75, p = 0, t-test, 2 sided

Adverse events

Time frame: Adverse event data were prospectively collected from the first visit until 48 hours after the last study visit in all participants and until the resolution of any potential adverse event reported by a subject after a study procedure, up to 6 months.. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Allergic Asthmatics(AA)	1 of 22 (4.5%)	2 of 22 (9.1%)	0 of 22
Allergic Non-Asthmatics(ANA)	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Non-Allergic Non-Asthmatics(NANA)	0 of 4 (0%)	0 of 4 (0%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
UCSF Airway Clinical Research CenterLink provided by the sponsor.

Related trials for Asthma

RecruitingPhase 1
Pilot Study to Identify the Mediators and Inflammatory Cell Surface Receptors Involved in Allergic Airway Inflammation
Asthma
RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
Asthma, Mild Asthma
RecruitingPhase 3
A Study Assessing the Effect of Dupilumab on Inducing Clinical Remission in Asthma
Asthma Control
Active, not recruitingPhase 2/3
Local Antibiotic Delivery for Community Acquired Pneumonia
Community Acquired Pneumonia (CAP)
RecruitingPhase 2
A Study to Learn About the Study Medicine Called PF-07275315 in People With Moderate-To-Severe Asthma
Asthma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Prescott G Woodruff, MD, MPH principal investigator

University of California, San Francisco

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Segmental airway allergen challenge, Bronchoscopy and Methacholine challenge test in people with Asthma, run by Prescott Woodruff at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in Expression of Epithelial miRNAs (in Read Counts) 24 Hours After Allergen-challenge as Compared to 24 Hours After Diluent Challenge in Participants With Allergic Asthma (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02230189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2022.