AsthmaSEARCHNCT02791542
Sorting and Expression Profiling of Airway Cells From Humans (The SEARCH Study)
An observational study of Asthma, run by University of California, San Francisco at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2017to Mar 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy and asthmatic participants recruited from community advertising
Who may be able to join
- 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
- 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
Show all 9Show fewer
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
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.
Read the 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.
- Conditions
- Asthma
- Keywords
- Asthma
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Asthma | Participants with a history of asthma | |
| Healthy controls | Participants without a history of asthma | |
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: Between 1-12 weeks
Assessment of persistence of signatures of airway inflammation
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)
Measured: 1-12 weeks and at 10-14 months
Secondary outcomes (1)
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.
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.
Measured: Between 1-12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study startJan 2017
- Primary completionMar 2023
- Study completionMar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID)
- Responsible party
- Sponsor
- Investigators
- Nirav Bhakta, MD, PhD, Principal investigator, University of California, San FranciscoPrescott Woodruff, MD, MPH, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02791542
- Sponsor's protocol ID
- 16-18550
- Other IDs
- R01HL138424, U19AI077439
- Acronym
- SEARCH
- Status last verified
- Feb 2024
- First submitted
- 1 Jun 2016
- Last updated
- 5 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorting and Expression Profiling of Airway Cells From Humans (The SEARCH Study)
- ClinicalTrials.gov ID
- NCT02791542
- Acronym / sponsor ID
- SEARCH / 16-18550
- Conditions
- Asthma
- Keywords
- Asthma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Jan 2017 (actual)
- Primary completion
- Mar 2023 (actual)
- Study completion
- Mar 2023 (actual)
- First posted
- 6 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Asthma | – | –Participants with a history of asthma |
| Healthy controls | – | –Participants without a history of asthma |
| 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy and asthmatic participants recruited from community advertising
Key inclusion criteria (9 listed)
- 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
- Male and female subjects between the ages of 18 and 70 years
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Assessment of persistence of signatures of airway inflammation
Time frame: 1-12 weeks and at 10-14 months
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)
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2024.
- Individual participant dataSharing planned: No
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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.
Nirav Bhakta, MD, PhD principal investigator
University of California, San Francisco
Prescott 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?
An observational study of Asthma, run by University of California, San Francisco 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 9 inclusion and 7 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 5 Feb 2024. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
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). 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?
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 5 Feb 2024.