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CompletedNCT02791542SEARCHUpdated Feb 5, 2024

Sorting and Expression Profiling of Airway Cells From Humans (The SEARCH Study)

An observational study in Asthma, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-05.

Sponsored by University of California, San Francisco · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
32
Ages
18 Years to 70 Years
Sex
All
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Study 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. 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.

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Conditions studied

  • Asthma

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Keywords

  • Asthma
03

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 32 is below the median of 150 across 970 observational studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Healthy and asthmatic participants recruited from community advertising

Eligibility criteria

Inclusion Criteria (Healthy participants):

  1. Male and female subjects between the ages of 18 and 70 years
  2. Ability to provide written informed consent and ability to comply with the requirements of the study
  3. No hyperreactivity to methacholine (PC20 FEV1 Methacholine >16 mg/mL)
  4. No history of allergic rhinitis/seasonal allergies

Inclusion Criteria (Asthmatic participants):

  1. Male and female subjects between the ages of 18 and 70 years
  2. Ability to provide written informed consent and ability to comply with the requirements of the study
  3. History of asthma
  4. No use of oral or inhaled corticosteroids for the treatment of asthma during the past 6 weeks
  5. Hyperreactivity to methacholine (PC20 FEV1 Methacholine \< 8 mg/ml)

Exclusion Criteria:

The same exclusion criteria will apply to both Sub-studies.

  1. 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
  2. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study
  3. Subjects with a history of lung disease other than asthma
  4. 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
  5. Prior esophageal hernia surgery.
  6. Current participation in an investigational drug trial
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Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
32 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

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What researchers measure

Primary outcomes

  1. 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.

    Time frame: Between 1-12 weeks

  2. 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)

    Time frame: 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.

    Time frame: Between 1-12 weeks

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Study locations

1 site
  • University of California, San Francisco
    San Francisco, California 94143, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 5, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02791542
Lead sponsor
University of California, San Francisco
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
Jun 6, 2016
Start date
Jan 2017
Primary completion
Mar 2023
Completion
Mar 2023
Last update
Feb 5, 2024

Study contacts

Nirav Bhakta, MD, PhD
principal investigator · University of California, San Francisco
Prescott Woodruff, MD, MPH
principal investigator · University of California, San Francisco

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.

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