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

NCT02791542 | Completed

• 3 other identifiers: 16-18550R01HL138424U19AI077439
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Asthma

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  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.

  Between 1-12 weeks

Study Arms (4)

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy and asthmatic participants recruited from community advertising

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Bronchial brushes and lavage Sputum, induced Whole blood Urine Serum Plasma

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Nirav Bhakta, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Prescott Woodruff, MD, MPH

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 6, 2016
• Study Start: January 1, 2017
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)