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

Study Contact Backup

Study Locations

    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco

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):

  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

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
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 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
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)
1-12 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
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.
Between 1-12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

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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