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

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ClinicalTrials.gov Identifier: NCT02791542
Recruitment Status : Recruiting
First Posted : June 6, 2016
Last Update Posted : April 18, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
University of California, San Francisco

Brief 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.

Condition or disease
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.

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Study Type : Observational
Estimated Enrollment : 70 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Sorting and Expression Profiling of Airway Cells From Humans (The SEARCH Study)
Actual Study Start Date : January 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

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



Primary Outcome Measures :
  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. [ 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.

  2. 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)


Secondary Outcome Measures :
  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. [ 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.


Biospecimen Retention:   Samples With DNA
Bronchial brushes and lavage Sputum, induced Whole blood Urine Serum Plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy and asthmatic participants recruited from community advertising
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. Current participation in an investigational drug trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02791542


Contacts
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Contact: Amira Elfhafsi, BS 415-502-2892 amira.elhafsi@ucsf.edu
Contact: Christine P Nguyen, BS, CCRP 415-476-3824 christine.nguyen@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Amira Elhafsi, BS    415-502-2892    amira.elhafsi@ucsf.edu   
Contact: Christine P Nguyen, BS, CCRP    415-476-3824    christine.nguyen@ucsf.edu   
Sponsors and Collaborators
University of California, San Francisco
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Nirav Bhakta, MD, PhD University of California, San Francisco
Principal Investigator: Prescott Woodruff, MD, MPH University of California, San Francisco

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02791542     History of Changes
Other Study ID Numbers: 16-18550
R01HL138424 ( U.S. NIH Grant/Contract )
U19AI077439 ( U.S. NIH Grant/Contract )
First Posted: June 6, 2016    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by University of California, San Francisco:
Asthma
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases