- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02791542
Sorting and Expression Profiling of Airway Cells From Humans (The SEARCH Study) (SEARCH)
February 1, 2024 updated by: University of California, San Francisco
This will be a single site, mechanistic study of asthmatic subjects and healthy, non-asthmatic controls involving a baseline characterization visit and a research bronchoscopy visit.
We will identify differences in airway epithelial epigenetic enhancer signatures in asthma, by analyzing freshly isolated airway epithelial cells from healthy controls and from well-characterized subjects with asthma.
Study Overview
Status
Completed
Conditions
Detailed Description
The airway epithelium is critical for normal lung function and changes in the epithelium are central to the development of asthma.
Precise regulation of gene transcription is essential for airway epithelial cell differentiation and transcription changes lead to many abnormalities seen in asthma.
Despite the dominant role of enhancers in regulating transcription, little is known about how these DNA regulatory elements control airway epithelial cell transcription or about how enhancer activity differs in asthma compared to health.
Closing this knowledge gap will have a major impact on our understanding of normal epithelial development and asthma.
In addition, enhancer-based approaches for reprogramming the airway epithelium promise to be powerful tools for dissecting mechanism that will set the stage for developing a new class of precisely targeted treatments for asthma.
Our overall goals are to identify enhancers that are important in regulation of key airway epithelial cell genes, to determine how enhancer activity changes in asthma, and to develop approaches for targeting the activity of these enhancers.
Study Type
Observational
Enrollment (Actual)
32
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Devin Roberts, BA
- Phone Number: 628-233-1233
- Email: devin.roberts@ucsf.edu
Study Contact Backup
- Name: Christine P Nguyen, BS, CCRP
- Phone Number: 415-476-3824
- Email: christine.nguyen@ucsf.edu
Study Locations
-
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California
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San Francisco, California, United States, 94143
- University of California, San Francisco
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Sampling Method
Non-Probability Sample
Study Population
Healthy and asthmatic participants recruited from community advertising
Description
Inclusion Criteria (Healthy participants):
- Male and female subjects between the ages of 18 and 70 years
- Ability to provide written informed consent and ability to comply with the requirements of the study
- No hyperreactivity to methacholine (PC20 FEV1 Methacholine >16 mg/mL)
- No history of allergic rhinitis/seasonal allergies
Inclusion Criteria (Asthmatic participants):
- Male and female subjects between the ages of 18 and 70 years
- Ability to provide written informed consent and ability to comply with the requirements of the study
- History of asthma
- No use of oral or inhaled corticosteroids for the treatment of asthma during the past 6 weeks
- Hyperreactivity to methacholine (PC20 FEV1 Methacholine < 8 mg/ml)
Exclusion Criteria:
The same exclusion criteria will apply to both Sub-studies.
- Current smokers, defined by (a) >5 cigarettes smoked in past 12 months, and (b) ≤ 8 weeks since last time smoking; or former smokers who have a total smoking history ≥10 pack-years
- Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
- Subjects with a history of lung disease other than asthma
- Subjects with a history of a medical disease, which in the opinion of the Investigator may put the subject at extra risk from study-related procedures or because the disease may influence the results of the study
- Prior esophageal hernia surgery.
- Current participation in an investigational drug trial
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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Asthma
Participants with a history of asthma
|
Healthy controls
Participants without a history of asthma
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Asthma Bronchoscopy sub-group
Participants with a history of asthma who will undergo the same procedures as other healthy controls with the addition of bronchoscopy
|
Healthy Bronchoscopy sub-group
Participants without a history of asthma who will undergo the same procedures as other healthy controls with the addition of bronchoscopy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measure the genomic location of enhancers in genes previously found to be differentially expressed in asthma vs health using H3K27ac ChIP-seq and ATAC-seq on airway epithelial brushings.
Time Frame: Between 1-12 weeks
|
We previously identified changes in epithelial gene expression in individuals with asthma.
To identify candidate enhancers that account for these changes, we will use Drop-seq, ChIPseq and ATAC-seq to analyze freshly isolated airway epithelial cells from healthy controls and from well-characterized subjects with asthma.
|
Between 1-12 weeks
|
Assessment of persistence of signatures of airway inflammation
Time Frame: 1-12 weeks and at 10-14 months
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Perform epithelial brush gene expression profiling and sputum induction on longitudinal samples obtained at 12 months after the initial bronchoscopy, to assess stability of type-2 and non-type-2 pathways that are dysregulated in asthma.
(Achieved via the PISA sub-study)
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1-12 weeks and at 10-14 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measure gene expression by RNA sequencing in both airway brushes and BAL cells for assessment of non-type-2 pathways differentially expressed in asthma vs health.
Time Frame: Between 1-12 weeks
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Perform bronchoalveolar lavage (BAL) cell flow cytometry and epithelial brush gene expression profiling to look for non-type-2 pathways that are dysregulated in asthma.
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Between 1-12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Nirav Bhakta, MD, PhD, University of California, San Francisco
- Principal Investigator: Prescott Woodruff, MD, MPH, University of California, San Francisco
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 1, 2017
Primary Completion (Actual)
March 1, 2023
Study Completion (Actual)
March 1, 2023
Study Registration Dates
First Submitted
June 1, 2016
First Submitted That Met QC Criteria
June 1, 2016
First Posted (Estimated)
June 6, 2016
Study Record Updates
Last Update Posted (Estimated)
February 5, 2024
Last Update Submitted That Met QC Criteria
February 1, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16-18550
- U19AI077439 (U.S. NIH Grant/Contract)
- R01HL138424 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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